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Biomedical subjects

T E Carey

Publications and source records attributed to T E Carey.

At least 19 recordsLinked to original sources
PubMed1992

Alterations in antigen expression in superficial bladder cancer.

Bladder cancer can be viewed as a prototype for carcinogen-induced neoplasia. This has been demonstrated experimentally in a variety of systems and in man through epidemiological studies of occupational exposure to putative carcinogens. The natural history of this neoplasm demonstrates recurrence in time and space, i.e., multifocal disease. This clinical scenario is precisely what would be expected if a target tissue, e.g., urothelium, was continuously exposed to a weak carcinogen. The detection of gross disease is clinically easy. However, the ability to intervene at early stages and monitor the success of this treatment requires the definition of early markers for bladder cancer. Integrins are a family of cell surface proteins, many of which function as receptors for extracellular matrix components. Normal epithelial cells express the integrin alpha 6 beta 4 in association with an anchoring structure known as the hemidesmosome. Urothelium expresses alpha 6 beta 4 on the basal layer of cells similar to the distribution seen on other epithelial surfaces. Even early stages of bladder cancer demonstrate an alteration in the expression of this integrin. Low-stage bladder tumors express alpha 6 beta 4 diffusely throughout the tumor as well as at the invading margin. Altered expression of alpha 6 beta 4 may be an early marker for bladder cancer which may contribute to an invasive phenotype. A second potential marker is detected by DD23, an IgG1 murine monoclonal antibody triggered by the immunization of a BALB/c mouse with a fresh human bladder tumor specimen. The antigen detected by DD23 is not present on normal urothelial specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Serial studies of autologous antibody reactivity to squamous cell carcinoma of the head and neck.

In previous studies we evaluated the incidence and specificity of autologous antibody reactivity against squamous cell carcinoma of the head and neck (SCCHN). We were able to demonstrate that autologous antibody reactivity is present in native sera but was usually of too low a titer to allow further analysis. Dissociation of immune complexes by acidification and ultrafiltration of serum augmented autologous antibody reactivity in nine out of nine autologous systems tested. Native antibody and antibody derived from immune complexes produced by the host and reactive with autologous tumor cells may be directed against physiologically relevant antigens. Therefore, correlations of antibody titers with clinical course may provide insight into the nature of the host response to cancer. In the present analysis, serological studies of six patients with SCCHN were performed with serum samples obtained over many months. Results of serial serological assays were correlated to tumor progression and clinical course. Fluctuations in autologous antibody reactivity were noted over time. In four cases, rises in autologous antibody titers preceded the clinical diagnosis of recurrence by several months. Drops in autologous antibody reactivity were noted in two cases following surgery or radiation therapy. In two cases of long-term survivors, no correlation between antibody reactivity and clinical course was noted. Specificity analysis of the six autologous systems demonstrated reactivity against autologous and allogeneic SCCHN as well as melanoma cell lines. These sera did not react with glioma, neuroblastoma, renal cell, breast, bladder and colon carcinoma cell lines nor with fetal calf serum, pooled lymphocytes, red blood cells and platelets. Autologous serial serological studies may provide a means by which to evaluate the host/tumor relationship in patients with SCCHN.

Aged↗
PubMed1992

Overexpression of the A9 antigen/alpha 6 beta 4 integrin in head and neck cancer.

A tumor-associated antigen detected by monoclonal antibody UM-A9 raised against a cultured cell line from a patient with an aggressive SCC of the oral cavity has been defined. The A9 antigen is abnormally expressed in squamous cancers, with loss of basal polarization and increased intensity of expression distinguishing malignant from normal cells. A minority of cultured SCC cell lines and about one third of fresh tumors exhibit polarized A9 expression. The increased intensity and loss of polarized expression of A9 antigen in recurrent and metastatic tumor cell lines when compared with primary or early tumor cell lines from the same patients indicated an association of altered expression with tumor progression. When A9 expression was evaluated in frozen tumor sections, three patterns of expression representing increasing intensity and loss of polarization were observed. Patients whose tumors exhibited the most intense A9 antigen expression had a higher rate of early relapse than patients whose tumors exhibited low intensity and polar expression. Loss of blood group antigen expression was also associated with poor prognosis, and together high A9 antigen expression and loss of blood group defined a group of patients at high risk of early relapse. The A9 antigen is immunologically and biochemically identical to the alpha 6 beta 4 integrin. The association of high expression of the A9/alpha 6 beta 4 integrin as a prognostic factor is supported by similar findings with a mouse model system. The mouse tumor-associated antigen, TSP-180, which is also an alpha 6 beta 4 integrin, distinguishes highly metastatic tumor cells from nonmetastatic variants of the same tumor line. In SCC, the alpha 6 beta 4 integrin contributes to attachment to laminin since anti-alpha 6 subunit specific antibody blocks cell attachment and only the beta 4 subunit is found in association with the alpha 6 subunit in these cells. Similar findings were obtained in colon carcinomas. Antibodies and peptides that block laminin attachment may lead to the development of antimetastatic agents for squamous carcinomas. The beta 4 subunit is unique from other integrins in that it has an unusually long cytoplasmic domain, the function of which is not known. The beta 4 subunit is heavily phosphorylated under conditions that favor anchoring and terminal differentiation in normal keratinocytes. Paradoxically the beta 4 subunit is also heavily phosphorylated in tumor cells, which are highly migratory and immortalized.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Neoplasm↗
PubMed1992

Tumor antigen phenotype, biologic staging, and prognosis in head and neck squamous carcinoma.

Prior studies of alterations in tumor expression of normal blood group antigens and A9/alpha 6 beta 4 integrin, an extracellular matrix receptor, have suggested that these immunohistologic markers reflect the biologic aggressiveness of head and neck squamous carcinomas. To confirm these preliminary observations, prospective long-term follow-up of 82 previously untreated head and neck squamous carcinoma patients was performed. All patients were treated with conventional therapy. Median follow-up was 57 months. Tumor immunohistology for ABH blood group and A9/alpha 6 beta 4 integrin expression was performed and correlated with measures of host cellular immunity, disease-free survival, and overall survival. Loss of blood group expression and high A9/alpha 6 beta 4 integrin expression were each directly related to an increased frequency of early tumor recurrence. The combination of both variables was significantly associated with both disease-free (P = .029) and overall survival (P = .05). Increased expression of A9/alpha 6 beta 4 was associated with impaired T-lymphocyte function (P = .005), and loss of blood group expression was associated with decreased peripheral blood levels of CD8+ T-lymphocytes (P = .013). The findings suggest that these phenotypic characteristics of antigen expression in head and neck squamous carcinomas are important markers of biologically aggressive cancers and impaired host immune response. The clinical use of these biologic staging parameters in the initial assessment of patients should allow selection of more aggressive primary treatment strategies for individual patients.

ABO Blood-Group System↗
PubMed1992

Regulation of expression and phosphorylation of A9/alpha 6 beta 4 integrin in normal and neoplastic keratinocytes.

The A9 antigen is a basement membrane antigen of normal squamous epithelial cells that is strongly expressed in many squamous carcinomas. High expression of this antigen is associated with early relapse in squamous cell carcinomas of the head and neck. We now know that the A9 antigen is structurally, immunologically, and functionally similar to the alpha 6 beta 4 integrin that has been shown to be linked to metastatic behavior in murine tumor models. The alpha 6 and beta 4 genes have been cloned and sequenced, and a model has been constructed from the deduced amino acid composition. In this study we present a hypothetical model and use it to design experiments to assess the factors that influence the expression of the A9/alpha 6 beta 4 integrin in normal and malignant keratinocytes. High calcium induces down regulation of A9/alpha 6 beta 4 antigen in normal but not malignant keratinocytes within 24 hours. Although calcium can down-regulate beta 4 message in tumor cells in the absence of epidermal growth factor (EGF), transcription of beta 4 increased in the tumor cells under the conditions we used for assessing antigen expression (calcium plus EGF). Retinoic acid also stimulated transcription of beta 4 in tumor cells, but this was partially inhibited by the presence of high calcium. Phosphorylation of the beta 4 chain was stimulated by epidermal growth factor and calcium in normal keratinocytes, but in the malignant cells phosphorylation was constant regardless of the culture conditions. Our results indicate that high expression of the alpha 6 beta 4 integrin is associated with conditions that favor migration and undifferentiated proliferation of normal keratinocytes and that malignant keratinocytes differ from normal keratinocytes by constitutive phosphorylation of beta 4 and by failure to downregulate beta 4 transcription in response to calcium in the presence of EGF.

Antigens, Neoplasm↗
PubMed1991

In vitro radiation resistance among cell lines established from patients with squamous cell carcinoma of the head and neck.

Twenty-five squamous cell carcinoma (SCC) cell lines from 20 patients with head and neck cancer were assessed for radiosensitivity in vitro using a 96-well plate assay. Four non-SCC lines were also tested. Radiation sensitivity of individual cell lines was compared using the area under the survival curve (AUC) as a measure of the mean inactivation dose. Tumor lines were tested with either a cobalt-60 (60Co) gamma-irradiator having a dose rate of 100 cGy/minute or with a 4-meV photon beam having a dose rate of 200 cGy/minute. The mean AUC of the 25 SCC cell lines was 188 +/- 7 (SEM) cGy (range, 100 to 250 cGy) whereas the four non-SCC lines had a mean AUC of 225 +/- 9 cGy. The SCC cell lines with mean inactivation dose values greater than 188 cGy were classified as relatively radioresistant whereas those with values less than 188 cGy were considered relatively radiosensitive. In seven cases SCC cell lines were derived from patients who had already received radiation therapy. In four of these cases the tumor cell lines were radioresistant (AUC, 210 to 250) but in the other three cases the tumor lines were radiosensitive (AUC, 160 to 180). Thus, failure of a tumor to respond to radiation did not always select for radioresistant cells. The mean of the AUC for cell lines from previously irradiated patients (197 +/- 11 cGy) did not differ significantly from that of the cell lines from patients who received no prior radiation therapy (182 +/- 9 cGy). However, among radiation-resistant lines those from the four previously irradiated patients were significantly more resistant (mean AUC = 235 +/- 9) than seven other radioresistant lines from nonirradiated patients (mean AUC, 208 +/- 4) (P = 0.0194). In four cases more than one cell line was derived from different tumor specimens in the same patient. In each of these cases the lines from the same patients were similar to one another in their degree of radioresistance. Based on these observations the authors conclude that the degree of in vitro radiation resistance is an inherent property of some squamous cell tumors.

Adult↗
PubMed1991

The A9 antigen associated with aggressive human squamous carcinoma is structurally and functionally similar to the newly defined integrin alpha 6 beta 4.

We previously reported that altered expression of the A9 antigen (defined by monoclonal antibody UM-A9) is a predictive marker of early recurrence and progression of squamous cell carcinoma (SCC). In normal squamous cells A9 expression is limited to the site of contact with the basement membrane in vivo and the culture surface in vitro, whereas aggressive SCCs exhibit loss of polarity and increased intensity of A9 expression. The potential relationship of the A9 antigen to structures known to be involved in cell adhesion was analyzed by immunobiochemical and cell adhesion assays. UM-A9 precipitates a complex of protein chains reminiscent of the alpha and beta heterodimer glycoproteins that characterize the integrin family of extracellular matrix receptors. Proteins were isolated from A9-positive cells using UM-A9 and well-defined antibodies specific for integrin alpha and beta chains. UM-A9, anti-alpha 6, and anti-beta 4 monoclonal antibodies (mAbs) all precipitated proteins with comparable electrophoretic mobilities. Furthermore, UM-A9 mAb precleared the SCC alpha 6 beta 4 integrin complex isolated with anti-alpha 6 or anti-beta 4 mAbs but not that isolated by anti-beta 1 mAb. The isoelectric points of the A9 complex chains were consistent with those reported for alpha 6 and beta 4. Three of the polypeptide chains (140, 175, and 205 kDa) precipitated by UM-A9 showed peptide homology to one another and to the beta 4 chain precipitated by mAb 439-9B. The A9/alpha 6 subunit is composed of 125- and 30-kDa chains and was distinguished from beta 4 and beta 1 chains by its peptide map and isoelectric point. UM-A9 binds to an epitope common to the beta 4 subunits since in pulse-chase analysis the beta 4 species are precipitated at an early time point, whereas detection of alpha-subunit synthesis is detected during assembly of the mature complex. Immunoprecipitation and preclearing experiments demonstrated that in SCC the alpha 6 subunit is associated primarily with the beta 4 species and not with the 130-kDa beta 1 subunit. In cell adhesion assays on extracellular matrix proteins, the alpha 6-specific GoH3 mAb inhibited binding of SCC to laminin, suggesting that alpha 6 beta 4 may function as a laminin receptor in SCC. These data and our prior observations showing an association between altered A9 expression and early recurrence in SCC provide the first evidence that altered expression of alpha 6 beta 4 integrin is associated with the clinical behavior of human squamous cell carcinomas.

Antigens, Neoplasm↗
PubMed1991

Consistent chromosome abnormalities in squamous cell carcinoma of the vulva.

Six squamous cell carcinomas of the vulva (SCV) were karyotyped in short-term culture and in early passages as established cell lines. Each tumor was cytogenetically distinct, contained multiple chromosome rearrangements, and was karyotypically stable in culture. Heterogeneity within individual tumors was manifested by the presence of more than one clonal population, but the clones within each tumor were closely related to one another. Seven consistent chromosome abnormalities found in five of the six tumors were: losses of 3p14-cen, 8pter-p11, 22q13.1-q13.2, and the short arm of the inactive X; chromosome gains involving 3q25-qter and 11q21; and rearrangement breakpoints at 5cen-q12. Ten additional chromosome changes were observed in four of the six SCVs, and together, 22 changes occurred in at least three of the tumors. Two specific losses, 10q23-q25 and 18q22-q23, were present in all four tumors that exhibited biologically aggressive behavior in vivo, but these losses were not found in the tumors of the two long-term survivors. These findings indicate that: 1) SCVs are genetically complex, but homogeneous; 2) loss of 18q22-q23 and loss of 10q23-q25 may be associated with a poor prognosis; and 3) development and progression of SCV appear to result from cumulative effects of altered gene dosage at multiple, consistent loci.

Adult↗
PubMed1991

Monoclonal antibodies to inner ear antigens: II. Antigens expressed in sensory cell stereocilia.

To develop biological reagents for investigating structure-function relationships in the organ of Corti, we have raised monoclonal antibodies, (MAb) to inner ear tissues. Our first series of antibodies prepared after intrasplenic immunization of mice with guinea pig tissues, identified antigens restricted to supporting cell structures, but no hair cell specific antibodies were developed [Zajic et al., Hear. Res. 52, 59-72, 1991]. In this report we describe the isolation, binding specificity and initial characterization of the stereocilia-binding monoclonal antibodies, KHRI-4, and KHRI-5. Mice were immunized with avian, amphibian and mammalian sensory hair cell-containing tissues and antibodies were screened for selective binding to cochlear extracts in ELISA. In the inner ear, KHRI-4 and KHRI-5 bind specifically to stereocilia in both avian and mammalian cochlear and vestibular tissue preparations using immunofluorescence and immunoperoxidase assays. In other tissues only certain cells of mesothelial origin, such as smooth muscle in gut and the arteriolar vasculature, were stained by KHRI-4 indicating that the antigenic structure defined by this antibody has limited distribution. KHRI-5 binding could be detected in other tissues only at high antibody concentrations suggesting that the gene product identified by this antibody is also weakly expressed in other cell lineages. Western blot analysis showed that KHRI-4 and -5 detect different protein complexes. KHRI-4 identifies an antigenic structure common to gut, cochlea, vestibular tissue and cultured fibroblasts consisting of a approximately 195 and a 230 kDa heterodimer designated p195/230. KHRI-5 binds to a prominent approximately 200-210 kDa band in Western blots of cochlear tissues, gut and fibroblasts. In immunoprecipitation experiments, KHRI-5 precipitated three proteins of Mr approximately 200-210, 230 and 260 kDa indicating that the approximately 200-210 kDa protein carrying the epitope for this antibody is a member of a heterotrimer complex. Our results show that these protein complexes are structural components of stereocilia and that the same proteins are arrayed in conjunction with the actin stress fibers of cultured mesothelial cells. Thus, they are likely to be important for maintaining the actin structure of stereocilia essential to transduction in sensory hair cells.

Animals↗
PubMed1991

Monoclonal antibodies to inner ear antigens: I. Antigens expressed by supporting cells of the guinea pig cochlea.

Murine monoclonal antibodies against guinea pig cochlear epithelium were generated with the goal of identifying cochlea-specific antigens and elucidating their function. To compensate for the limited amount of cochlear tissue, intrasplenic immunization was used. Hybridoma supernatants were screened by ELISA for antibody production and for binding to homogenates from cochlea, liver, lung, kidney and brain. Hybrids producing antibody to cochlea were subcloned and tested immunocytochemically against frozen sections and surface preparations of paraformaldehyde-fixed cochlear tissue. KHRI-1, a low titer IgM antibody stained only Hensen cells. KHRI-2, also an IgM antibody, stained tectorial membrane, cells of the spiral limbus, cells bordering the space of Nuel, Hensen cells and the root cells of the spiral prominence. KHRI-3, an IgG1 antibody, stained the phalangeal processes of outer pillar cells and the apical portion of phalangeal processes of Deiters' cells in a distinctive wine goblet pattern on surface preparations. KHRI-3 antibody also reacted with peripheral nerves and pia mater of brain in unfixed frozen sections but the antigenic site was not stable to fixation in contrast to the epitope detected in the cochlea. In Western blots of detergent extracts from cochlea KHRI-3 stained a broad tissue-specific band of Mr 70-75 kDa; a narrower band of Mr 68-70 kDa was identified by KHRI-3 in extracts of tongue and brain. KHRI-1 and KHRI-2 did not detect any proteins in Western blots. The monoclonal antibodies KHRI-1, -2, and -3 which define epitopes expressed by discrete populations of supporting cells in the inner ear should be useful in characterizing the nature and function of cellular structures in the cochlea.

Animals↗
PubMed1991

Human papillomavirus DNA sequences in cell lines derived from head and neck squamous cell carcinomas.

There is increasing evidence that human papillomaviruses (HPV) have a casual role in some neoplasms in human beings. As examples, DNA of HPV types 16, 18, and 31 are frequently present in genital cancers in humans. Recently, oncogenic HPV types have also been identified in neoplasms of the head and neck, including verrucous carcinoma of the larynx, squamous cell carcinomas of the oral cavity and larynx, and inverted papillomas of the nose. These findings and our resource of an extensive panel of head and neck squamous cell carcinoma (HNSCC) cell lines led us to begin to investigate how frequently HPV DNA was present in these tumor cell lines. For initial analysis, twenty-two HNSCC cell lines derived from 20 patients' tumors were selected as representative of our tumor cell line panel with respect to diversity of primary site, tumor stage, patient age, sex, and clinical course. For Southern analysis, cell line DNA was tested for hybridization with DNA probes for HPV types 6, 11, 16, 18, and 31. Polymerase chain reaction (PCR) analysis was also performed on five tumor cell lines using types 6, 11, 16, 18, and 52 as probes. Southern blot analysis revealed HPV-specific signals in two of the 22 HNSCC cell lines tested. One of these, UM-SCC-23, was HPV 31 positive, which to our knowledge is the first identification of HPV 31 in HNSCC. UM-SCC-63, the other HPV-positive tumor identified by Southern analysis, hybridized with both type 18 and 31. Of the five tumor cell lines tested with PCR, two were HPV positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck.

Monoclonal antibody UM-A9 identifies an antigen found on the basal surface of epithelial cells and expressed on all of the squamous cell carcinomas (SCC) that we have tested. In a previous study, we showed that cell lines from metastatic or recurrent SCC exhibit stronger expression of the A9 cell membrane antigen than cell lines from the primary tumor of the same donors, suggesting that this marker is associated with tumor progression. Loss of expression in tumor tissue of normal A, B, and H (ABH) blood group antigens has also been linked to clinical behavior in some epithelial cancers. To determine the prognostic significance of these antigen markers, we prospectively evaluated tissue specimens for expression of these markers in a group of 82 consecutive, previously untreated patients with SCC of the head and neck. Three patterns corresponding to strong (pattern 1), intermediate (pattern 2), or weak (pattern 3) A9 antigen expression were observed. Fifty-eight percent of the patients whose tumors had pattern 1 A9 antigen expression and 78% of the patients with loss of blood group antigen had early relapse, compared with only 34% of those with A9 antigen pattern 2 or 3 (P = .042) and 37% of those whose tumors expressed the mature ABH blood group antigen (P = .012). The combination of A9 pattern and ABH blood group antigen expression in tumor tissue was the variable most strongly associated with duration of disease-free survival, even after adjustment for the traditional prognostic factors of tumor site, stage, and TNM classification. Loss of blood group was the most significant single variable associated with early recurrence, but among patients whose tumors retained ABH blood group antigen expression, the A9 pattern distinguished good and poor prognostic groups. To our knowledge, our study is the first to demonstrate that differences in blood group antigen expression are significantly correlated with disease-free survival in SCC of the head and neck. We have initiated a study (a) to determine the relationship of the A9 antigen and the blood group antigens with clinical response of the tumors and (b) to determine whether these markers should be used as prognostic indicators.

ABO Blood-Group System↗
PubMed1990

Phenotypic characterization, karyotype analysis and in vitro tamoxifen sensitivity of new ER-negative vulvar carcinoma cell lines, UM-SCV-1A and UM-SCV-1B.

Two cell lines (University of Michigan squamous carcinoma of the vulva UM-SCV-1A and UM-SCV-1B) were established from the primary tumor and a malignant pleural effusion of a 62-year-old woman. Both tumor specimens grew vigorously in vitro and could be passaged after only 14 and 10 days in culture, respectively. Both cell lines undergo 3 population doublings in 4 days, reaching saturation densities of 5 x 10(5) cells/cm2, and have been carried through more than 30 in vitro passages. In nude mice the cultured cells initially formed tumors but these regressed 2-3 weeks after inoculation. The regressing mouse tumors consisted of poorly differentiated squamous carcinoma surrounded by an inflammatory lymphoid infiltrate. The UM-SCV-1 cell lines express membrane antigens typically displayed by squamous-cell carcinomas. These include the HLA class-1 light chain beta 2-microglobulin, pemphigus, pemphigoid, and the alpha 6 beta 4 integrin defined by the UM-A9 monoclonal antibody (MAb). In contrast to the A431 vulvar carcinoma, these tumor lines do not have amplified expression of the epidermal growth factor (EGF) receptor. Although tissue from the primary tumor contained low levels of estrogen receptor activity, no receptor activity was detected in the cell lines. Nevertheless, both lines were sensitive to growth inhibition by tamoxifen. This effect was not reversible by estradiol, indicating an estrogen-receptor-independent mechanism. The tumors were both hypotetraploid, contained the same chromosome rearrangements and had stable karyotypes in vitro. Each contained inv(1)(p36.3q32.1), del(4)(q12), dic(4;11)(q12;p11.2), i(5p), der(6)t(3;6)(q25.1;p21.1), several rearrangements involving chromosomes 8 and 14, + i(13), i(18p), a dicentric t(11;19), and 2 or 3 unidentified markers. Since the karyotypes of both tumors were the same, no major karyotypic change was associated with metastatic spread. These paired primary and metastatic SCC lines from an unusually aggressive vulvar carcinoma provide an in vitro model for analysis of the biological basis of this tumor's behavior.

Animals↗
PubMed1990

Calcium regulation of antigen expression on normal and malignant human squamous cells in vitro.

In vitro, normal keratinocytes exhibit undifferentiated morphologic features and proliferate for multiple passages in low-calcium medium (less than or equal to 0.3 mmol/L) whereas, in high-calcium medium (greater than or equal to 1.0 mmol/L), these cells assume differentiation characteristics, begin to stratify, and eventually cease proliferating. In contrast, malignant keratinocytes grow well in high-calcium medium. Expression of pemphigus vulgaris antigen, a squamous cell marker, is altered on cultured normal keratinocytes by calcium. In this study we compared the effects of calcium levels on expression of cell surface antigens by UM-SCC-38, a human squamous carcinoma cell line, and normal keratinocytes cultured from newborn foreskin. Pemphigus, pemphigoid, beta 2-microglobulin antigens, as well as the epidermal growth factor receptor and the A9 germinal epithelial cell basement membrane squamous carcinoma antigen were examined. Pemphigus antigen was strongly expressed on normal and malignant cells in high-calcium but not low-calcium medium. Calcium concentration did not affect the expression of any of the other antigens tested. Thus, although calcium induces differentiation and eventual loss of proliferative capacity in normal but not malignant keratinocytes in vitro, we were unable to demonstrate differences in pemphigus vulgaris antigen expression that might be linked to the growth inhibitory effects induced by high calcium levels in nontransformed epithelial cells in culture.

Antigens, Surface↗
PubMed1990

Establishment and characterization of UM-EC-2, a tamoxifen-sensitive, estrogen receptor-negative human endometrial carcinoma cell line.

UM-EC-2 was established from a patient with poorly differentiated stage IB endometrial carcinoma. This cell line produces tumors in nude mice that have the same histological features as the patient's tumor. UM-EC-2 cells express b2-microglobulin, the epidermal growth factor receptor (EGF), and the H blood group antigen. This membrane antigen phenotype is consistent with cells of human endometrial origin. The karyotype of UM-EC-2 is fairly complex, with rearrangements affecting all chromosomes except 3, 10, 14, 19, and 20. There were two populations of cells, a hyperdiploid population with a modal number of 53-55 and a hypertetraploid population with a modal number of 109. A postulated sequence of events before and after tetraploidization is suggested based on the number of copies of individual chromosomes and rearrangements. Comparison of the UM-EC-2 karyotype to that of UM-EC-1 (a previously described line from a different patient with endometrial carcinoma) revealed that the two lines share eight very similar chromosome changes, which include loss of most of chromosome 4, breakpoints affecting proximal bands on 8p, loss of most of 9q, a breakpoint at 12q22, loss of 13q, breakpoints in proximal bands on 18q, and a breakpoint at 22p11. These changes may represent nonrandom chromosome abnormalities in poorly differentiated endometrial cancer. Estrogen (ER) and progesterone (PgR) receptors were not detected in either the primary tumor or the cell line. Nevertheless, UM-EC-2 cells were very sensitive to growth inhibition by tamoxifen (TAM) in vitro. One micromolar TAM caused 50% inhibition of cell growth, 2.5 microM caused cytostasis, and 5 microM TAM was cytotoxic, killing all cells after 5-7 days of exposure to the drug. Paradoxically, 100 nM estradiol (E2) caused a moderate increase in the growth of the cells but it did not prevent or reverse growth inhibitory effects of TAM. These findings support the concept that in some tumors TAM causes growth inhibition by an ER-independent mechanism. UM-EC-2 cells were also sensitive to growth regulation by EGF. Thus, these cells provide a new in vitro model of human endometrial cancer in which the roles of both TAM and EGF as growth regulatory substances can be investigated.

Antigens, Neoplasm↗
PubMed1990

Comparison of antigen expression on normal urothelial cells in tissue section and tissue culture.

Antigenic characterization of urothelial cells cultured from normal adult ureter was performed. These cells were cultured using a simplified isolation and culture technique and a commercially available serum-free medium. The cells growing in these cultures had epithelioid morphology and normal quantities of DNA. The antigen expression on these cultured normal urothelial cells was evaluated using a panel of monoclonal antibodies: 5G6.4, AN43, URO-5, anti-keratin and anti-blood group antibodies, and 425 (anti-epidermal growth factor receptor). Lower levels of anti-A and AN43 binding on cultured cells were observed than are seen on urothelial cells in sections of normal ureter, while the binding of anti-blood group H, 5G6.4, and URO-5 was unchanged. Binding of anti-epidermal growth factor receptor antibody 425 was improved if the cells were grown in medium lacking epidermal growth factor. These results confirm the urothelial origin of these cultured urothelial cells but indicate that some antigenic differences between cultured normal urothelial cells and urothelial cells in situ in the normal ureter exist.

ABO Blood-Group System↗
PubMed1990

Modulation of squamous carcinoma cell growth, morphology, adhesiveness and extracellular matrix production by interferon-gamma and tumor necrosis factor-alpha.

Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were examined for effects on human squamous carcinoma cells. IFN-gamma inhibited proliferation at concentrations between 100 and 1,500 units/ml and the inhibitory effects were potentiated by TNF-alpha. Inhibition of cell growth was not accompanied by cytotoxicity. Combined treatment with the two cytokines also inhibited cell-substrate adhesion and altered the morphology of the cells. The treated cells were large and flattened. These morphological features are similar to those that have been previously described for normal keratinocytes induced to differentiate by a variety of means. The changes in biological properties were accompanied by alterations in production of extracellular matrix components - e.g., fibronectin and thrombospondin. Synthesis of both components was decreased following treatment. The cytokine-induced alterations in squamous carcinoma cell properties were fully reversible. These findings indicate that malignant squamous epithelial cells may be similar to their normal counterparts in their responses to IFN-gamma and TNF-alpha. In the malignant cells, however, these cytokines do not appear to induce permanent phenotypic changes.

Carcinoma, Squamous Cell↗