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At least 19 recordsLinked to original sources
PubMed1991

C. L. Oakley Lecture (1991). Cell adhesion and epithelial differentiation.

The differentiated function of epithelial tissues is dependent on the molecules which mediate the cohesion and polarization of the epithelium. Separate molecular families are responsible for the adhesion between adjacent cells and the adhesion between cells and the substratum. Using the kidney as a model of epithelial differentiation it has been shown that the assembly of a basal lamina containing the glycoprotein laminin and cadherin mediated intercellular adhesion are key events. The Wilms' tumour anti-oncogene plays a regulatory role in renal epithelial differentiation. Tissue modeling and tumour formation are both accompanied by reduced cell adhesion molecule function.

Cell Adhesion↗
PubMed1992

Behavior of epithelial differentiation antigens (carcinoembryonic antigen, epithelial membrane antigen, keratin and cytokeratin) in transitional cell carcinomas of the bladder.

Results of an immunohistochemical study in normal urothelium and transitional cell carcinomas of the bladder are presented. Paraffin-embedded material was confronted with immunoantisera against carcinoembryonic antigen (CEA), keratin (K), cytokeratin (CK) and epithelial membrane antigen (EMA). Immunohistochemical findings confirm the changes in reactivity of dysplastic urothelium and carcinoma in situ for CEA, CK and EMA, in comparison with normal urothelium. Statistically significant differences were also found, depending upon tumor stage, in staining of transitional cell carcinomas for K and CK. Expression of CK correlated with the tumor differentiation grade: normal urothelium and well-differentiated carcinomas showed a specific pattern of immunostaining for the basal cells, this pattern being lost in poorly differentiated carcinomas.

Adult↗
PubMed1991

Epithelial differentiation in the absence of extracellular matrix.

To investigate the regulation of epithelial differentiation, normal human epidermal keratinocytes were cultured floating on the surface of culture medium without attachment to a solid substrate. Keratinocytes spread out on the surface of the medium, proliferated and differentiated either into several flat lacy sheets 1 to 3 cells thick (on medium containing 0.15 mM calcium) or formed one single aggregate of cells from 5 to 15 cells in thickness on medium containing 1.15 mM calcium. The cell aggregates demonstrated a pattern of ordered epithelial differentiation. Levels of progressive differentiation resembling the structure of normal human epidermis were identified by light microscopy, immunohistochemistry, and electron microscopy. Differentiation proceeded from cells at the air side toward cells at the medium side with basal appearing cells on the air side and keratinocytes expressing filaggrin and involucrin on the side toward the medium. These results demonstrate that organized epithelial differentiation can occur in the absence of extracellular matrix. In contrast with other air-liquid interface cultures, epithelial differentiation in the absence of extracellular matrix progresses from air towards medium.

Cell Adhesion↗
PubMed1991

Mammary epithelial differentiation in vitro: minimum requirements for a functional response to hormonal stimulation.

Mammary epithelial differentiation is the culmination of responses to a complex sequence of hormonal stimuli. An in vitro model for this process should retain the basic features of in vivo epithelial differentiation. The IM-2 mouse mammary cell line responds to lactogenic hormone stimulation by synthesizing the milk protein beta-casein. Epithelial and fibroblastic clones derived from IM-2 lack this ability, but cocultures of these clones regain responsiveness to lactogenic hormone stimulation. Studies of the epithelial cell clone 31E under various culture conditions reveal that the role of fibroblastic cells in supporting synthesis and secretion of beta-casein can be supplanted by culture in filter chambers without addition of exogenous extracellular matrix components. Electron microscopic and immunofluorescence studies show that, under these conditions, 31E epithelial cells exhibit the morphology and intercellular organization characteristic of mammary epithelium. Transepithelial electrical resistance measurements indicate that the cells are well polarized. Analysis of glucose metabolism is consistent with this polarization; glucose is utilized from the basal chamber, and lactate is excreted into the basal chamber. Immunoblot analysis demonstrates the vectorial protein secretion expected of polarized mammary epithelium: laminin is secreted into the basal chamber, whereas beta-casein is secreted into the apical chamber in response to lactogenic hormone stimulation from the lower chamber. Thus, the maintenance of a polarized intercellular organization that permits access of the basolateral cell surface to nutrients is sufficient for a pure culture of an established mammary epithelial cell clone to retain differentiated epithelial function in vitro.

Animals↗
PubMed1991

Modulation of xanthine dehydrogenase and oxidase activities during the hormonal induction of vaginal epithelial differentiation in ovariectomized mice.

The modulation of xanthine dehydrogenase/oxidase (XD/XO) activities in vaginal epithelium as a function of estrogen- and progesterone-induced differentiation was investigated in ovariectomized SENCAR mice. The vaginal epithelium of ovariectomized mice consisted of one or two cell layers. Intraperitoneal administration of 20 micrograms 17 beta-estradiol stimulated vaginal hyperplasia, and orthokeratinization. In contrast, although i.p. administration of 2.5 mg progesterone induced hyperplasia, it caused mucification of surface cells. Relative to ovariectomized control mice, vaginal XO specific activities were significantly elevated within 48 h of estradiol treatment and reached a maximum (285%-330% of control) 24-48 h later. The changes in XO specific activity correlated with the appearance of granular and horny layers in the epithelium, and reflected increases in both tissue XD content and the conversion of XD to XO. Approximately 45% of total XD + XO activity was XO in control mice. In contrast, 80% of total activity was contributed by XO in mice 72 h or 96 h after 17 beta-estradiol treatment. In marked contrast, vaginal XO + XD and XO specific activities, and XO/XD + XO ratios were unaffected in ovariectomized mice treated with progesterone. Collectively, these studies suggest that the expression of XD, and the conversion of XD to XO in vaginal epithelium are differentiation-specific, and characteristic of the orthokeratinization pathway of differentiation.

Animals↗
PubMed1976

Evaluation of vitamin A analogs in modulating epithelial differentiation of 13-day chick embryo metatarsal skin explants.

Seventeen vitamin A compounds were evaluated in organ culture for activity in altering epithelial differentiation of metatarsal skin explants from 13-day-old chick embryos. The explants keratinized in 6 to 8 days and, when cultured in the presence of beta-retinoic acid (RA), inhibition of keratinization occurred and a mucous metaplasia developed. A cyclopentenyl analog of retinoic acid was approximately 10-fold more effective than RA in producing mucous metaplasia. Six other analogs exhibited about the same activity as RA: trimethylmethoxyphenyl analog of retinoic acids, alpha-retinoic acid, 13-cis-retinoic acid, methyl retinoate, ethyl retinoate, and N-ethylretinamide. The following 5 vitamin A compounds were about one-fourth as effective as RA: the trimethylmethoxyphenyl analog of ethylretinamide, the phenyl analog of retinoic acid, the trimethylmethoxyphenyl analog of ethyl retinoate, beta-retinyl acetate, and retinol. The furyl analog of retinoic acid and N,N-diethylretinamide were approximately one-tenth and one-fifteenth less effective than RA in inhibiting keratinization. The analog, alpha-retinyl acetate, was about one-hundredth as effective as RA and the pyridyl analog of retinoic acid (2.5 X 10(-5) M) did not inhibit keratinization. Since the property of altering epithelial differentiation may be a fundamental requirement for the prophylaxis and/or treatment of malignant epithelial lesions, this system can be used to determine whether the new synthetic analogs of vitamin A are active in modulating epithelial differentiation.

Animals↗
PubMedDate not supplied

Malignant fibrous histiocytoma with epithelial differentiation?

A case of recurrent soft part sarcoma with focal areas showing epithelial differentiation in the right thigh in a 78-year-old woman is reported. The primary tumor consisted of myxoid areas and solid areas, in which relatively uniform epithelioid tumor cells were arranged in sheets, whereas pleomorphism and a storiform pattern appeared in the recurrent tumors. Thus this tumor was suspected to be a malignant fibrous histiocytoma. However, further studies showed unexpected ultrastructural and immunohistochemical features. Cytokeratin immunoreactivity and tonofilamentlike structures probably indicated epithelial differentiation of some tumor cells. From the clinical and histological findings, this tumor should be identified as a malignant fibrous histiocytoma with phenotypic expressions of epithelial cell.

Aged↗
PubMedDate not supplied

Ewing's sarcoma with epithelial differentiation: fine structural and immunocytochemical study.

A femoral Ewing's sarcoma from a 13 1/2-year-old girl with otherwise typical clinical and pathological features showed epithelial differentiation by electron microscopy and immunocytochemistry. The expression of keratin and the presence of tonofilaments in cells of this Ewing's sarcoma may enforce the hypothesis that Ewing's sarcoma derives from a multipotential primitive stem cell.

Adolescent↗
PubMed1985

Distribution of vimentin, cytokeratins, and desmosomal-plaque proteins in human nephroblastoma as revealed by specific antibodies: co-existence of cell groups of different degrees of epithelial differentiation.

The distribution of cytokeratins, desmosomal-plaque proteins (desmoplakins), and vimentin in nephroblastoma tissue was studied by immunofluorescence microscopy using specific antibodies. In undifferentiated blastema cells, desmosomes, as revealed by antibodies to desmoplakins, preceded the advent of significant amounts of cytokeratins, indicating that desmosomes are early and sensitive markers of epithelial differentiation. Cytokeratin-positive tumor cells were seen in the following distribution patterns: groups of loosely arranged and scattered cells containing only scant cytokeratin fibrils surrounded by negative stroma cells; focal accumulation of cytokeratin-positive cells with cytokeratin-specific cytoplasmic fibril meshwork staining; rosettes of cytokeratin-positive cells without formation of distinct lumina, showing concentration of cytokeratin staining in the center; tubules with distinct lumina made up of cytokeratin-positive cells, with cytokeratin staining concentrated in the subapical cell portions. In cytokeratin-positive cells, the numbers of desmoplakin-positive dots were generally increased; in well-formed tubules, enrichment of desmoplakin-positive spots, corresponding to the subapical skeletal disks, was most conspicuous. Vimentin was demonstrated in stromal areas, but also in blastema cells showing coexpression of desmosomes and vimentin filaments. Moreover, in certain blastema cells, an overlap of cytokeratin and vimentin immunostaining was observed. Epithelial cells of nephroblastoma tubules did not react with vimentin antibodies. Our results show that the appearance of desmosomal plaques, as demonstrated by antibodies to desmoplakins, may be a very early feature of epithelial differentiation, and they also emphasize the value of antibodies to desmoplakins in tumor cell typing and diagnosis.

Cell Differentiation↗
PubMedDate not supplied

Osteogenic sarcoma with epithelial differentiation.

This case report details an osteogenic sarcoma arising in a vertebra in which cytokeratin intermediate filaments were detected immunohistochemically with three different antibodies. This feature was present not only in the primary neoplasm but also in two local recurrences and a metastasis to the iliac bone. What is unique about this primary bone tumor, however, is the structural evidence for epithelial differentiation. Ultrastructurally, well-formed desmosomes and tonofilaments were present in all four surgically resected specimens. This tumor expands the list of soft tissue and bone tumors in which anomalous expression of intermediate filaments can occur but, more important, illustrates that changes in genetic expression of neoplasia of mesenchymal origin can result in paradoxic epithelial differentiation.

Adult↗
PubMedDate not supplied

The long-term effect of clomiphene citrate on vaginal epithelial differentiation in the mouse.

Clomiphene citrate, administered to the neonatal mouse during cervicovaginal epithelial differentiation, is associated with subsequent adenosis. Similar lack of neonatal transformation of columnar to squamous epithelium occurs after diethylstilbestrol. Mouse neonatally exposed to diethylstilbestrol have a high incidence of reproductive tract tumors in later life. In this study Balb/c neonates were exposed to clomiphene citrate, maintained with controls, and killed at 52, 56, and 60 weeks. Cervicovaginal histology was studied by light microscopy. In all control animals only mature squamous epithelium was seen (44/44). After clomiphene citrate, at 52 weeks, 3/10 animals had other than mature squamous epithelium identified. One of these genital tracts contained adenosis. At 56 weeks only mature squamous epithelium was seen (11/11), and at 60 weeks immature squamous epithelium was identified in 1 of 10 animals. In no study animal (0/31) was there any evidence of tumor development. This differs from the high incidence of reproductive tract tumor seen in the mouse after neonatal diethylstilbestrol exposure.

Animals↗
PubMed1988

Cooperation between the polyomavirus middle-T-antigen gene and the human c-myc oncogene in a rat thyroid epithelial differentiated cell line: model of in vitro progression.

Two rat thyroid epithelial differentiated cell lines, PC Cl 3 and PC myc, were infected with the polyoma murine leukemia virus (PyMLV) carrying the Middle-T-antigen gene of polyomavirus. After infection, both cell lines acquired the typical markers of neoplastic transformation; however, the PC myc cells showed a greater malignant phenotype. Furthermore, the thyroid differentiated functions were completely suppressed in PC myc cells transformed by PyMLV, whereas they were, at least partially, retained in PC Cl 3 cells transformed by PyMLV, and in particular, thyroglobulin synthesis and secretion were not affected at all. Since no differences in the expression of the middle-T-antigen gene were observed in the two PyMLV-transformed cell lines, the different properties shown by these two infected cell lines must be ascribed to the expression of the c-myc oncogene.

Animals↗
PubMed1992

Epithelial differentiation in gliomas, meningiomas and choroid plexus papillomas.

The immunohistological findings using antibodies to different intermediate filaments (glial fibrillary acidic protein, vimentin and two types of cytokeratin) and epithelial membrane antigen are described in 89 gliomas, 19 meningiomas and 8 choroid plexus papillomas (CPPs) from adult patients. All the patients had total or subtotal surgical excision of their tumours with clinical follow up for between 3 and 7 years. The immunohistological results were correlated with the histological features and patient survival. Tumours other than low grade astrocytomas, oligodendrogliomas and anaplastic ependymomas expressed one or more epithelial markers. This immunohistological evidence of epithelial differentiation in the absence of histological epithelial features in gliomas confirms that the two are not necessarily correlated. It is concluded that the expression of epithelial markers in some intradural tumours may reflect aberrant differentiation related to the degree of anaplasia in poorly differentiated astrocytomas and glioblastomas. All the patients with anaplastic epithelial marker-positive gliomas died within 1 year, whereas only 68% of patients with marker-negative tumours died within the follow-up period. In ependymomas and meningiomas, the expression of epithelial markers may reflect their histogenesis, while in malignant CPPs such expression could denote either their aberrant differentiation or histogenetic derivation.

Adolescent↗
PubMed1992

Intermediate filaments and epithelial differentiation of male rat embryonic gonad.

The presence and distribution of desmin, vimentin, cytokeratin, and laminin in the gonads of developing male rat embryos (11-17 days) were studied by immunocytochemistry. The findings were correlated with morphological changes of the cells and with the formation of basement membranes, as determined by electron microscopy. The surface epithelial and subepithelial cells of the meesonephros in the prospective gonadal region contained desmin. At the onset of gonadal development, vimentin appeared in the somatic cells of the thickening surface epithelium, which formed the gonadal ridge. Desmin disappeared and cytokeratins appeared in the Sertoli precursor cells at the inception of their epithelial differentiation. Simultaneously, the prospective Sertoli cells became polarized during their assembly into epithelial cell aggregates; the aggregates then fused and formed elongated testicular cords. The epithelial cell differentiation was accompanied by a deposition of basement membrane material around the cords and by an increase of desmin in the cells immediately around the cords. With further differentiation of the testicular cords, some cytokeratins from the Sertoli cells, but not from the cells of the rete cords, disappeared. On the other hand, other cytokeratin polypeptides and vimentin remained in the fetal Sertoli cells. The surface cell layer slowly differentiated towards a proper epithelium after the basic formation of the testicular cords and interstitium. Desmin and vimentin persisted in the interstitial cells throughout the entire study period. The early differentiation of the gonad is apparently under a general sex-independent initiation program. The developmental changes in intermediate filaments offer an opportunity for the further analysis of their general role in early organogenesis. In light of the genetic theory of testicular differentiation, the functions of the regulatory factor(s) include specific organization of cord cells, histological organization into looping cords rather than separated follicles, and male development of the interstitium, surface epithelium and tunica albuginea.

Animals↗
PubMed1988

Epithelial-mesenchymal interactions in intestinal epithelial differentiation.

The complex morphogenetic events and the concomitant structural and functional differentiation of intestinal progenitor cells are dependent on tissue interactions. Several experimental models of hetero-species or -topic recombinants between epithelial and mesenchymal anlagen are described. They enabled us to elucidate the respective roles of these tissue components in morphogenesis, epithelial differentiation, and hormone-elicited responses. Among the mechanisms of tissue interactions, the possible mediation of permissive and instructive information via the extracellular matrix is postulated. Arguments in favor of this are provided by the observation of compositional changes in matrix molecules during intestinal development and differentiation. On the other hand, in vitro experimental data emphasize the role of actual contacts between epithelial and mesenchymal cell populations and the importance of the mesenchyme for basement membrane formation.

Animals↗
PubMed1992

Cytokeratins as epithelial differentiation markers in premalignant and malignant oral lesions.

The keratin expression pattern in oral stratified epithelium is related to the cellular differentiation level. The normal pattern shows the keratin pair K5 and K14 in the stratum basale whereas K1 and K10, or K4 and K13, are the two pairs associated with differentiating suprabasal cells. Monoclonal and polyclonal antibodies to individual keratins (K10, K13 and K14) were used in a two-color immunofluorescence staining method to study their coexpression in single cells. Altered keratin expression in premalignant and malignant lesions indicated abnormal differentiation. Monospecific keratin antibodies were suggested to be useful for evaluation of epithelial differentiation changes in oral dysplasias and oral squamous cell carcinomas.

Biomarkers, Tumor↗