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M Zöller

Publications and source records attributed to M Zöller.

At least 73 records · Page 4Linked to original sources
PubMed1997

Contrasting effects of K8 and K18 on stabilizing K19 expression, cell motility and tumorigenicity in the BSp73 adenocarcinoma.

The co-expression of vimentin and keratin-type intermediate filaments in the same cell was often reported to correlate with increased invasiveness and a more aggressive tumorigenic phenotype. To address the possible physiological relevance of these observations, we transfected simple keratins (K8 and 18) either individually, or in combination, into a tumorigenic but non-metastatic pancreatic adenocarcinoma that expresses vimentin but no keratins. Expression of K8 resulted in the stabilization of endogenous K19 in these cells, and formation of keratin filaments containing K8 and K19. Transfection of K18 yielded unstable K18 protein, but K18 could be stabilized when K8 was co-expressed in the same cells. Clones expressing K18 alone, or together with K8, displayed a reduced ability to grow in soft agar and decreased motility when compared to control, or K8/19 expressing cells. Moreover, K18 expressing cells were dramatically inhibited in their ability to form tumors when injected into syngeneic animals. The extent of suppression in the tumorigenicity of these cells correlated with the level of K18 expressed by these cells. The results show that K18 expression in cells may result in the suppression of the motile and tumorigenic abilities of this adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Transient absence of CD44 expression and delay in development by anti-CD44 treatment during ontogeny: a surrogate of an inducible knockout?

Because the lack of some adhesion molecules induced by site-directed mutagenesis has been described to be lethal, whereas the lack of others apparently has no effect, we were interested in seeing whether the developing organism might gradually adapt to the absence of adhesion molecules. Therefore, we chose a form of transient interference by i.v. injection of antibody into pregnant rats. As a model, we selected CD44, which has been reported to play a key role during embryogenesis. Rats received either an antibody recognizing an epitope on the CD44 standard isoform (CD44s) or on exon v6 (CD44v6). In the presence of anti-CD44s, delivery was frequently delayed, and intrauterine abortions were often observed. The fetuses were smaller, particularly the anlage of the hair follicle of the whisker, and the formation of alveoli in the lung, of the tubular system of the kidney, and of villi in the gut was delayed. The development of fetuses receiving anti-CD44v6 was hampered until days 16-18 of gestation. Immunodetection revealed a weaker expression of the target molecules at the implantation site and the complete absence of CD44s and CD44v6 expression in fetal tissue until day 12. During the late stages of gestation, the expression pattern of CD44 resembled that of 2-3-day-younger fetuses of untreated rats. Interestingly, degradation of hyaluronate was also delayed, particularly in the kidney. Thus, the diaplacental antibody passage was very efficient and should make it possible to obtain a clearly defined and differentiated concept of the requirements for the CD44 molecule during ontogeny and also for fail-safe mechanisms. Both experiences may be missed in the knockout proper.

Animals↗
PubMed1996

Accelerated immune response in transgenic mice expressing rat CD44v4-v7 on T cells.

Splice variants of the glycoprotein CD44 (CD44v) that confer metastatic behavior to noninvasively growing rat tumor cells are transiently expressed on lymphocytes during activation. A mAb directed against an epitope encoded by CD44 exon v6 blocks both metastasis formations and lymphocyte activation, implicating CD44v in normal immune function. To explore the nature of this function of CD44v, transgenic mice were generated that constitutively express rat CD44v4-v7 on thymocytes and peripheral T cells. The number of lymphocytes as well as the distribution of lymphocyte subpopulations were similar in nontransgenic and rat CD44v4-v7 transgenic mice. T cells of the transgenic mice, however, responded faster to activating stimuli, particularly during primary stimulations with T cell mitogens and T-dependent Ags in vivo and in vitro. This accelerated response depended on the expression of the transgene product, since a rat CD44v6-specific Ab reverted the response profiles of the transgenic mice to those of nontransgenic mice. Since the transgene gained in vivo and in vitro functional activity only upon antigenic stimulation, it is likely that CD44 variant isoforms are involved in the process of signal transduction during lymphocyte activation.

Animals↗
PubMed1996

Expression of CD44 splice variants in normal respiratory epithelium and bronchial carcinomas: no evidence for altered CD44 splicing in metastasis.

Expression of alternatively spliced CD44 adhesion molecules has been implicated in metastatic spread of various rodent and human tumors. To determine whether specific CD44 splice variants contribute to metastatic spread of bronchial cancers, we compared the expression of CD44 splice variants in normal bronchial epithelium and bronchial cancers, including tumors which already spread to regional lymph nodes or distant organs. Variant CD44 expression was analysed by immunohistochemistry using variant exon-specific monoclonal antibodies. The precise composition of CD44 transcripts was delineated by exon-specific RT-PCR. The concurring data obtained by both methods revealed that high levels of standard CD44 and variants v5 and v6 as well as low levels of variants v7 and v10 are expressed both in normal bronchial epithelium and squamous cell lung cancers. No CD44 expression was observed in the highly metastatic small cell lung cancers and adenocarcinomas with the exception of bronchioalveolar cancers showing weak expression of standard CD44. These data suggest that expression of alternatively spliced CD44 molecules in the bronchial tract is related to the distinct differentiation of the respiratory epithelium. No correlation between expression of specific CD44 splice variants and metastasis of bronchial cancers was observed.

Alternative Splicing↗
PubMed1996

Expression of CD44 splice variants in squamous epithelia and squamous cell carcinomas of the head and neck.

Splice variants of the adhesion molecule CD44 have been described as essential for the lymphatic spread of rat tumour cells and are claimed to be involved in the metastatic spread of several human tumours. Immunohistochemistry has been used to analyse the expression pattern of CD44 standard (CD44s) and variant (CD44v) isoforms in normal and dysplastic squamous epithelia, as well as in primary and metastatic squamous cell carcinomas (SCCs), which spread predominantly by way of the lymphatic system. Frozen sections of squamous epithelia and of squamous cell carcinomas were stained with a panel of monoclonal antibodies recognizing epitopes of CD44s as well as of the variant exons v5, v6, v7, v7-v8, and v10. The stratum basale and stratum suprabasale of squamous epithelia stained with all antibodies; the stratum spinosum stained with anti-CD44v5, anti-CD44v6, anti-CD44v7-8 and anti-CD44v10; the lower layers of the stratum corneum stained with anti-CD44v5. This expression profile was seen in epithelia of the lip, the tongue, the gingiva, the hard palate, the floor of the mouth, the buccal mucosa, and the pharynx. The same pattern of expression was also noted in dysplastic epithelia, but expression of the variant exons v7, v8, and v10 was significantly downregulated in primary squamous cell carcinomas and was not detected at all in the majority of metastasis-derived specimens. Expression of CD44v5 and CD44v6, on the other hand, was mainly unaltered. Thus, epithelial cell layers representing different stages of differentiation express distinct sets of CD44 variant isoforms, where especially exons v8-v10 might be required for the maintenance of the structural integrity of squamous epithelium. Downregulation of these exons on tumour cells could indicate that they are irrelevant for tumour progression or may even hamper infiltration of surrounding tissue or of lymphatics.

Adult↗
PubMed1996

Requirement for CD44 in proliferation and homing of hematopoietic precursor cells.

The hematopoietic form of the adhesion molecule CD44 is known to be involved in lymphocyte maturation and homing. To define lineage and stage of maturation, which requires expression of CD44, murine long-term bone marrow cultures were established. Stroma formation and proliferation of early as well as committed erythroid, myeloid, and lymphoid progenitors were evaluated under the influence of monoclonal anti-CD44 antibodies. Although the formation of stromal elements was not affected, formation of cobblestone areas was completely abolished. [3H]thymidine suicide confirmed that anti-CD44 treatment interfered with the proliferation of early and committed hematopoietic progenitor cells. In addition, homing and seeding of bone marrow cells was impaired by anti-CD44. The data are indicative of a dual functional mode of CD44 in adhesion and proliferation of hematopoietic progenitors and confirm an essential requirement for the molecule in early stages of hematopoiesis.

Adipose Tissue↗
PubMed1996

Expression of CD44 splice variants in human skin and epidermal tumours.

Splice variants of the adhesion molecule CD44 (CD44v) are important in the lymphatic spread of rat carcinoma cells. In several human tumours expression of CD44v correlates with tumour progression. However, little is known about the physiological functions of distinct variant exons. Here we report on the immunohistological evaluation of CD44 expression in normal human skin and epidermal tumours which do not metastasise, or do so vary rarely. Frozen tissues were stained with a panel of monoclonal antibodies, recognizing epitopes of the CD44 standard isoform, as well as of variant exons v5, v6, v7, v7-v8 and v10. Stratum basale and spinosum as well as the root shaft of hairs reacted strongly with the whole panel of anti-CD44 antibodies. Stratum corneum, acinar cells of sebaceous and eccrine sweat glands stained with anti-CD44v5, anti-CD44v6 and anti-CD44v7, but not with anti-CD44v10, the latter recognizing the "epithelial isoform" (CD44v8-v10) of CD44. Ductal cells of glands and apocrine glands did not express CD44v. Compared with its expression in normal human skin, CD44v expression was reduced in basal cell carcinoma and squamous cell carcinoma of the skin. This was particularly true of CD44v10. The expression of CD44v in normal skin and dermal appendages indicates that not all combinations of variant exons are involved in tumour progression. Since the epithelial isoform is particularly downregulated in basal cell carcinoma and squamous cell carcinoma of the skin, it is unlikely that exons v8-v10 play a role in tumour progression. Rather, they may be of functional importance in maintenance of the epidermal structure.

Animals↗
PubMed1996

Development of a bispecific F(ab')2 conjugate against the complement receptor CR3 of macrophages and a variant CD44 antigen of rat pancreatic adenocarcinoma for redirecting macrophage-mediated tumor cytotoxicity.

A bispecific F(ab')2 antibody conjugate (BAC) was constructed against the complement receptor CR3 of macrophages and variant CD44 (CD44v6) antigen of rat pancreatic adenocarcinoma cells to redirect macrophage-mediated tumor cytotoxicity. The Fab' fragments of monoclonal antibodies (mAb) 1.1ASML and OX42, recognizing the CD44v6 and the CR3 antigens respectively, were chemically coupled at the hinge region using 5,5'-dithiobis(2-nitrobenzoate). The BAC was characterized in vitro for its specific, dual binding capacity to CD44v6 and CR3 antigens. Although the monovalence of the BAC resulted in lower avidities to both the antigens as expected, it was still able to form stable cross-linkages between tumor cells and macrophages in culture leading to the formation of "clump-like" cell aggregates. The in vitro and in vivo tumor-targeting capacity of the BAC was compared with that of the parental antitumor mAb 1.1ASML, which mediates tumor killing by antibody-dependent cell cytotoxicity. These results showed that, even though the bivalent mAb 1.1ASML did not mediate stable cross-linking of target and effector cells, its Fc-receptor-mediated killing of tumor cells was more effective when compared to the BAC. Thus, this study strongly supports the hypothesis that firm persistent binding between effector and target cells per se is not as important as the choice of trigger molecule used for macrophage activation to redirect their tumor cytotoxic potential effectively.

Adenocarcinoma↗
PubMed1996

Expression of the CD44 variant isoforms 6 and 4/5 in breast cancer. Correlation with established prognostic parameters.

Eighty one invasive breast cancers were analysed immunohistochemically to detect if they expressed the adhesion molecules CD44 v6 and v4/5, and the results were evaluated using the semiquantitative IR-score. The results were further divided into four groups: negative, weak positive, moderate positive and strong positive. Fifteen benign breast tumors were also analysed. Sixty eight breast cancers were CD44v6 and v4/5 positive. T3 and T4 cancers showed statistically significant higher positive CD44 rates than T1 and T2 cancers (P < 0.05). We also found a statistically significant correlation between the estrogen receptor and the CD44 status and between the CD44 status and the cathepsin-D status, whereas no correlation between CD44 and the lymph node status, the M status, the grading of the tumors, the progesterone receptor and the menopausal status could be found. Eleven benign tumors were CD44v6 and v4/5 positive. We could not establish any correlation between the expression of CD44 and the metastasizing capacity of breast cancer.

Breast↗
PubMed1996

Expression of CD44 variant isoforms in peripheral blood leukocytes in malignant lymphoma and leukemia: inverse correlation between expression and tumor progression.

In a variety of human tumors, including high grade Non-Hodgkin's lymphoma (hgNHL), a linkage between expression of CD44 variant isoforms (CD44v) and tumor progression has been described. In search of an easily accessible diagnostic parameter, expression of CD44 standard (CD44s) and CD44 variant isoforms (exons v5, v6, v7 and v10) in peripheral blood lymphocytes (PBLs) of patients with hematological malignancies was evaluated by fluorescence activated cell scanning. The analysis of 30 blood samples of healthy donors and patients with non-malignant diseases and of 183 blood samples of patients with malignant hematological disorders revealed that only in patients with malignant disorders did a measurable proportion of PBLs express CD44 variant isoforms, mostly exons v5, v6, v7 and, less frequently, exon v10. Elevated levels of CD44v expression were noted in PBLs of patients with acute and chronic myeloid leukemia (AML: 16%, CML: 25%), Hodgkin's disease (HD: 17%), multiple myeloma (MM: 22%), polycythemia vera (PV: 33%), acute lymphoid leukemia (ALL: 23%) and, most frequently, in PBLs of patients with non-Hodgkin's lymphoma (NHL:54%). CD44v expression was not restricted to the malignant phenotype, but instead was also noted in T cells, B cells and monocytes, preferentially in a subpopulation of large cells. Furthermore, expression of CD44v in PBLs was not linked to the histological grading or clinical staging. There was, however, an inverse correlation with tumor progression, whereas response to therapy was frequently accompanied by upregulation of CD44v. Thus, expression of CD44v in the PBLs of patients with NHL mainly reflected immune responsiveness. Since NHL manifests itself primarily in lymphoid organs, its progression is difficult to follow. Monitoring of CD44v in PBLs could be used as an additional and convenient parameter for surveying the course of disease.

Adult↗
PubMed1996

Transient expression of CD44 variant isoforms in the ontogeny of the rat: ectoderm-, endoderm- and mesoderm-derived cells express different exon combinations.

Expression on rat tumor cells of CD44 variant isoforms containing exons v4-v7 or v6-v7 has been described as sufficient for initiation of the metastatic cascade. The question arose as to whether physiological programs may be reactivated by particular CD44 isoforms. With this in mind, expression of mRNAs for the CD44 isoforms was surveyed during ontogeny of the rat. Using available monoclonal antibodies, expression of the CD44 standard isoform (CD44s) and of an epitope of CD44 exon v6 (CD44v6) were evaluated by immunohistology also. While CD44s was expressed in cells of all three germ layers, CD44v6 expression was restricted to distinct epithelial layers and cells of the hematopoietic system. During ontogeny, expression of CD44v6 was first noted in the neural tube and the leading epithelial layer of the limb buds. Later, anti-CD44v6 (1.1ASML) stained basal layers of the epidermis, the epithelium of the gut, and the acini of the submandibular gland. Strong, but transient expression of CD44v6 was seen during lung development, in hematopoietic stem cells of the liver, in thymic epithelia and early thymic immigrants. Expression in these organs was downregulated shortly before or after birth. As revealed by Southern blotting after use of the reverse transcriptase polymerase chain reaction (RT-PCR), most CD44v6-positive organs contained more than one CD44 variant isoform, and the expression patterns differed between individual organs. Hematopoietic cells preferentially expressed exons v4-v7, endodermal tissue exons v4-v10 and only in the epidermis were exons v1-v10 detected. The temporally regulated expression during ontogeny and the different exon compositions suggest a pivotal role of CD44 isoforms particularly in hematopoesis and in pattern formation by instructive epithelia.

Animals↗
PubMed1996

Developmentally regulated expression of metastasis-associated antigens in the rat.

The specificity of monoclonal antibodies (mABs) obtained after immunization with a metastasizing rat tumor line was evaluated by screening expression in a variety of nonmetastasizing and metastasizing rat tumor lines. mABs, which by immunohistology and Western blotting recognized metastasizing lines, were used to define the physiological expression of the corresponding antigens during ontogeny as well as in adult rats. From a panel of 12 mABs, 2 recognized structures on metastasizing and nonmetastasizing tumor lines, while 10 stained exclusively metastasizing lines. Five of the latter bound to tumor lines metastasizing either hematogenously or via the lymphatic system. All five recognized an epitope on CD44 variant exon v6. The five remaining mABs, recognizing four independent antigenic entities, only stained tumor lines metastasizing via the lymphatics. Surprisingly, these antigens were also detected in normal tissues: three on epithelial cells either widespread or of the upper gastrointestinal tract or the urogenital system, the fourth preferentially on epithelial cells, but also on nerves and hematopoietic precursor cells, and the fifth on many tissues and cells with a predominance of mesenchyme-derived structures. Notably, during ontogeny, expression on these five antigens was induced in different compartments of the developing fetal and/or maternal part of the placenta. The five newly described metastasis-associated antigens share with CD44v the absence of expression on nonmetastasizing tumor lines as well as expression on distinct, nontransformed cells and induction of expression during ontogeny. Thus, tumor progression may rather be initiated by inappropriate expression or up-regulation of genes, which do not display transforming features, than by de novo appearance of "metastasis genes." Accordingly, metastasizing tumor lines may be a valuable tool to identify developmentally regulated gene products.

Animals↗
PubMed1996

Expression of CD44 variant isoforms in malignant melanoma.

In a variety of human tumors, expression of splice variants of the adhesion molecule CD44 (CD44v) has been described as correlating with tumor progression. Here, we report on the expression of CD44v in melanocytes, nevi, primary melanomas, and cutaneous and lymph node metastases. Thirteen nevi, 65 primary melanomas of varying thickness, 39 cutaneous and 15 lymph node metastases, and melanocytes and a panel of melanoma lines were tested for surface expression of the standard form of CD44 and the variant exons v5, v6, v7, v7-v8, and v10 by immunohistology or fluorescence-activated cell sorting. Melanocytes did not express any variant isoform of CD44. However, nevi, as well as primary melanoma and melanoma metastases, stained to a varying degree with anti-CD44v5, anti-CD44v7-v8, and anti-CD44v10. Exons v6 and v7 were not detected on any of these tissue specimens. Compared with nevi, expression of exon v10 was up-regulated in thick primary tumors and skin metastases. Lymph node metastases displayed elevated levels of exon v5. Expression of CD44v in melanoma lines (n = 20) differed, inasmuch as many lines did not express variant isoforms; in particular, exon v10. Interestingly, however, the few CD44v5-positive melanoma lines metastasized in the nu/nu mouse. Because benign as well as malignant growth of melanocytes was accompanied by expression of CD44 variant isoforms, a linkage between expression of CD44 variant isoforms and malignant transformation or tumor progression was excluded. Considering the function of distinct isoforms, one might speculate that expression of exon CD44v5, which was up-regulated in lymph node metastases compared with nevi and primary melanoma, provided a growth stimulus. Exon v10 is present at high density in epidermal cells. The de novo expression of this exon in nevi and the increased expression in thick melanoma and skin metastases would be in line with the assumption of an anchoring advantage in the surrounding epidermal tissue.

Animals↗
PubMed1995

Multistep tumor targeting in nude mice using bispecific antibodies and a gallium chelate suitable for immunoscintigraphy with positron emission tomography.

To improve tumor:tissue ratios in immunoscintigraphy, a three-step targeting method has been developed. The reagents used were (a) a radioactive, low molecular weight chelate prepared from ionic gallium and a phenolic polyaminocarboxylic acid, which can be labeled either with the single-photon emitter 67Ga or with the short-lived positron emitter 68Ga (t1/2 = 68 min); (b) a bispecific monoclonal antibody (bs-mAb) synthesized from the F(ab)2 fragment of the 1.1ASML antibody specific for the glycoprotein CD44v associated with a rat pancreas carcinoma cell line and the F(ab') fragment of an antibody specific for the gallium chelate; and (c) the nonradioactive gallium chelate covalently coupled to transferrin, which served as a high molecular weight blocker to prevent binding of the radioactive gallium chelate to bs-mAbs in the circulation. Targeting experiments in tumor-bearing nude mice with different doses of bs-mAbs, blocker, and 67Ga chelate were adjusted to maximize tumor to tissue contrasts and tumor uptake. Compared with the biodistribution of the 131I-labeled, native 1.1ASML antibody 24 h postinjection, a schedule using 100 pmol bs-mab 24 h later 100 pmol blocker, 15 min later 16 pmol 67Ga chelate, 1 h later examination, increased tumor:blood and tumor: liver ratios by a factor of 5 while keeping the localization of radioactivity in the tumor constant (10.1% injected dose/g). High-contrast images using either 67Ga or 68Ga were obtained within 1 h. The targeting method described enables the use of the short-lived positron emitter 68Ga and thus allows the combination of an improved immunoscintigraphy and positron emission tomography.

Animals↗
PubMed1995

CD44: physiological expression of distinct isoforms as evidence for organ-specific metastasis formation.

Continuous progress has been achieved during recent decades in the therapy of metastasizing malignancies by improving chemotherapeutic strategies and new approaches in radiation therapy. Genetic manipulation of tumor cells and of the tumor fighting immune system is hoped to add significant contributions to curative interventions in disseminated tumors. That we are still far from eradicating death by malignant growth is due ultimately to our limited understanding of the cascade of events resulting in metastasis formation, which until recently was believed to rely on multiple rounds of mutation and selection processes. This implies an individually specific history of each metastatic tumor, which would rule out uniform diagnostic and therapeutic concepts. When it was noted in a rat tumor model that the transfer of cDNA of a single gene, a CD44 variant isoform (CD44v) covering the exons v4-v7, sufficed to initiate metastasis formation of a locally growing tumor, hope was created that a "metastogene" may have been identified. Although the idea of CD44v expression as a unifying concept for tumor progression was not sustained, the discovery of CD44v-initiated metastatic spread allowed a conceptually new hypothesis on tumor progression as a consequence of the reactivation of genetic programs of ontogeny, stem cell differentiation, and/or lymphocyte activation. Since distinct CD44 isoforms play an important role in these processes, unraveling the functions of this family of molecules can indeed provide a cornerstone in the understanding of tumor progression. This article summarizes briefly the present knowledge on known functions of CD44 isoforms with particular focus on parallels between physiological programs and tumor progression.

Animals↗
PubMed1995

Life expectancy, mortality and prognostic factors in neurofibromatosis type 1. A twelve-year follow-up of an epidemiological study in Göteborg, Sweden.

Neurofibromatosis type 1 (NF1) is a genetic disease with an extremely wide range of manifestations. As yet, the individual course of NF1 cannot be predicted, and it is uncertain to what extent the disorder is associated with increased mortality. In order to gain insights into these aspects, we have conducted a 12-year follow-up study of 70 adult NF1 patients in the city of Göteborg, Sweden, whereby life expectancy, mortality, causes of death and the prognostic value of clinical findings were investigated. Clinical examinations were made, and all available records, including medical files, death certificates, and autopsy reports were scrutinized. The survival in the NF1 cohort was compared to that in the general Swedish population. Twenty-two deaths occurred in the NF1 group, whereas 5.1 deaths were expected in the general Swedish population (p = < 0.001). The mean age at death was 61.6 years. Malignancy was found in 12 (55%) of the deceased (soft tissue sarcomas in 3, and carcinomas in 9). Severe complications related to NF1 were seen in 27%. Hypertension was significantly associated with increased mortality, as 10 out of 12 (83%) patients with hypertension died during the observation period. NF1 was associated with increased mortality due to malignancy and NF1-related complications.

Adult↗
PubMed1995

Expression of CD44 splice variants in normal, dysplastic, and neoplastic cervical epithelium.

Expression of splice variants of the CD44 adhesion molecule has been implicated in metastatic spread of various human tumor cells, including malignant lymphomas and colon, mammary, and gastric carcinomas, and has been correlated to a poor prognosis for the respective patients. To determine whether variant CD44 molecules might also contribute to the metastatic spread of cervical cancer, we analyzed the CD44 expression pattern in normal cervical epithelium and in low- and high-grade cervical dysplasia and compared it with invasive and metastasizing cervical cancers, including cell lines derived thereof by immunofluorescence and exon-specific PCR amplification of reverse-transcribed CD44 transcripts. We observed that normal cervical epithelium and dysplastic lesions express high levels of standard CD44 in the basal and spinous epithelial layers. CD44 molecules encompassing variant exons v5 and v6 are strongly expressed throughout the epithelium. Low levels of variants encompassing exon v7 are expressed in basal and spinous layers, with particular strength in the suprabasal layer. Low levels of epitopes encoded by v8 and v10 are expressed in the basal and spinous layers. In cervical cancers, including lymph node metastasis, we observed strong expression of v5 and v6, but almost no expression of v7, v8, and v10. Expression of the CD44 standard form appeared to be down-regulated in some cancers when compared to normal cervical epithelium. Thus, expression of variant CD44 molecules is related to distinct differentiation of mucosal squamous epithelia in the female genital tract. No correlation of the expression of variant CD44 isoforms, including the v7-v8 fusion epitope with tumor progression or lymphatic spread, was observed.

Alternative Splicing↗