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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uvomorulin (E-cadherin), a cell adhesion molecule, and Na+,K(+)-adenosine triphosphatase (ATPase), a marker protein of the basal-lateral cell membrane domains of polarized epithelial cells, were investigated in a group of mouse skin tumors induced by a two-stage chemical carcinogenesis protocol and in cell lines derived from mouse skin papillomas and squamous cell carcinomas (SCC). Although these two markers were present in benign tumors and in nontumorigenic cell lines, the Na+,K(+)-ATPase showed an altered pattern of distribution that included the presence of enzyme not only in the basolateral domain but also on the apical domain of the cell membrane of basal and spinous cells in well-differentiated squamous cell carcinomas (SCC). In higher grade SCC, a loss of Na+,K(+)-ATPase immunoreactivity was simultaneously detected with a marginal or absent expression of uvomorulin. The more differentiated SCC and papillomas expressed less uvomorulin immunoreactivity than normal epidermal cells. Both markers were seen in tumor cell lines that produced well-differentiated SCC after subcutaneous inoculation into nude mice. Neither Na+,K(+)-ATPase nor uvomorulin could be detected in cell lines that produced high grade, poorly differentiated SCC. Northern blots confirmed the absence of uvomorulin mRNA in these highly malignant cell lines. These data indicate that progression from premalignant papilloma to low-grade SCC and subsequently to high-grade SCC is accompanied by loss of epithelial cell polarity as detected by changes in Na+,K(+)-ATPase and by decreased or absent expression of uvomorulin in tumors and cell lines characterized by an advanced malignant phenotype.
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PMID:Alterations in the expression of uvomorulin and Na+,K(+)-adenosine triphosphatase during mouse skin tumor progression. 131 85

In order to elucidate the relationship of tumor invasion with the expression of E-cadherin and type IV collagen, I carried out immunohistochemical studies on a human gingival carcinoma xenograft line, GK-1, in nude mice. The transplanted tumors were divided into four stages of progression for examination at 5, 7, 10 and 15 weeks after transplantation based on the value of the labeling index for BrdU. The labeling index for BrdU showed its greatest value at seven weeks after transplantation. There was a marked decrease of E-cadherin expression in the tumors at seven weeks after transplantation, and the amount of expression negatively correlated with the labeling index. In addition, the expression of type IV collagen decreased, having a positive correlation with the expression of E-cadherin, and it became discontinuous and unstable. From the above findings, both the decreased expression of E-cadherin and the discontinuous expression of type IV collagen suggest that the tumor cells maintain high invasiveness.
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PMID:Tumor cell kinetics and expression of type IV collagen and E-cadherin in a human gingival carcinoma xenograft line in nude mice. 134 1

The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin (delta-cells), and pancreatic polypeptide (PP-cells) in a sequential order. The endocrine cells are believed to arise from a stem cell with neuronal traits. The developmental lineage from a common neuron-like progenitor is evidenced by: transient coexpression of more than one cell type-specific hormone in immature cells, expression of neuronal markers during islet cell development, and the pluripotentiality of clones of insulinoma cells to develop into cells expressing other islet cell hormones. The four mature endocrine cell types assume a particular organization within the islets of Langerhans in a process where cell adhesion molecules are involved. In this study we have analyzed the expression of neural cell adhesion molecule (NCAM) and cadherin molecules in neonatal, young, and adult rat islet cells as well as in glucagonomas and insulinomas derived from a pluripotent rat islet cell tumor. Whereas primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons. The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N-cadherin in brain. Insulinoma cells express E-cadherin but differ from primary islet cells by expressing a second cadherin molecule, which is similar to N-cadherin. The expression of NCAM and cadherin isoforms in the glucagonoma suggest that this transformed alpha-cell type has converted to an immature phenotype with strong neuronal traits, reflecting the early palce of glucagon-producing cells in the islet cell lineage. In contrast, insulinoma cells are more islet-like in their phenotype and show less neuronal traits.
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PMID:Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas. 140 10

Invasion, eventually leading to metastasis, is presented as the result of a balance between the activation of 2 sets of genes, coined i+ (invasion promotor) and i- (invasion suppressor) genes. Experiments in vitro have indicated that the homotypic homophilic epithelial cell--cell adhesion molecule E-cadherin (L-CAM; uvomorulin; cell CAM 120/80; Arc-1; rrl antigen) is an i- gene product. In several cell families, manipulation of E-cadherin at the level of the protein by antibody-mediated inactivation, at the level of the mRNA by antisense DNA transfection, and at the level of the genome by sense DNA transfection respectively resulted in induction and suppression of invasiveness. Nude mouse tumors from non-invasive homogeneously E-cadherin-positive cell populations were found to be invasive and metastatic. These tumors expressed E-cadherin in a heterogeneous manner, the undifferentiated cells being negative; but tumor-derived cells in culture were again E-cadherin-positive, indicating downregulation of this protein by host factors. Several types of human cancers showed a similar heterogeneity suggesting a relationship between downregulation of E-cadherin and invasion. Our current research focus is on the factors responsible for E-cadherin downregulation in experimental and human cancers.
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PMID:E-cadherin expression: a counterbalance for cancer cell invasion. 142 92

Cancer metastasis poses the greatest challenge to the eradication of malignancy. The majority of clinical and experimental evidence indicates that metastasis is a non-random, organ-specific process. Tumor cell interaction with endothelium and subendothelial matrix constitutes the most crucial factor in determining the organ preference of metastasis. A plethora of cell surface adhesion molecules, which encompass four major families (i.e., integrins, cadherins, immunoglobulins and selectins) and many other unclassified molecules, mediate tumor-host interactions. Adhesion molecules and adhesion processes are involved in most, if not all, of the intermediate steps of the metastatic cascade. Decreased E-cadherin expression and increased CD44 expression are clearly correlated with the acquisition of the invasive capacity of primary tumor cells. Similarly, altered expression pattern of many other adhesion molecules such as upregulated expression of the laminin receptors and depressed expression of fibronectin receptors (alpha 5 beta 1) appears to be involved in tumor cell invasion into the subendothelial matrix. Tumor cell-endothelium interactions involve several well-defined sequential steps that can be analyzed by the 'Docking and Locking' hypothesis at the molecular level. Tumor cell-matrix interactions are determined by the repertoire of adhesion receptors of tumor cells and the unique composition of organ-specific matrices. Our experimental data, together with others', suggest that the integrin alpha IIb beta 3 is one of the major players in these tumor-host interactions. Tumor-host interaction is a dynamic process which is constantly modulated by a host of factors including various cytokines, growth factors and arachidonate metabolites such as 12(S)-HETE. Delineation of the molecular mechanisms of tumor-host interactions may provide additional means to intervene in the metastatic process.
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PMID:Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix. 142 22

E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.
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PMID:Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. 151 67

Cadherins are a family of intercellular glycoproteins responsible for calcium-dependent cell adhesion and are currently divided into four types: epithelial (E), neuronal (N), placental (P), and vascular (V). Since cadherins are known to be indispensable for not only morphogenesis in the embryo but also maintenance of tumor cell nest, we examined the expression of E-cadherin in 31 meningiomas (11 syncytial, 12 transitional, 8 fibroblastic) and 3 arachnoid villi by immunoblot and immunohistochemical analyses. In the immunoblot analysis, E-cadherin was detected at the main band of Mr 124,000 in all of the arachnoid villi, as well as syncytial and transitional types of meningiomas, but not in the fibroblastic type. The immunohistochemical examination showed that E-cadherin was expressed at the cell borders of syncytial and transitional types, but the expression was absent in the fibroblastic type. Immunoelectron microscopy showed that E-cadherin was localized at the intermediate junctions in arachnoid villi, while it was detected diffusely at the cell surface in meningiomas. It is suggested from these data that the expression of E-cadherin might be closely related to the differentiation and organogenesis of meningioma cells.
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PMID:Immunohistochemical localization of cell adhesion molecule epithelial cadherin in human arachnoid villi and meningiomas. 155 Nov 27

Cadherins represent a family of Ca(2+)-dependent cell adhesion molecules involved in homotypic, homophilic cell-cell interactions. Recent studies have shown that the cadherins can play a role in invasive and metastatic behavior. Using the established Dunning R-3327 model system of serially transplantable rat prostate cancers, the expression of E- and P-cadherin in rat prostatic cancer was studied. Analysis within this system demonstrated that whereas E-cadherin was expressed in the normal rat prostate and the well- or moderately differentiated, noninvasive Dunning tumors, no expression, either at the mRNA or at the protein level, could be detected in the invasive sublines. Since not all invasive Dunning tumors studied have metastatic ability, these results suggest that a decreased expression of E-cadherin is correlated with invasive behavior rather than with metastatic ability. Recently, genetic instability occurred in an animal bearing the well differentiated, androgen-responsive, slow growing, nonmetastatic Dunning R-3327-H rat prostate cancer resulting in the progression to an anaplastic, androgen-independent, fast growing, highly metastatic state. This spontaneously arising tumor, termed the AT6 subline, in its original host was heterogeneously composed of both a well differentiated and an anaplastic population of cancer cells in which areas of squamous cell differentiation were occasionally observed. The original animal bearing this heterogeneous AT6 cancer developed multiple metastases, the lung metastases being heterogeneously composed of anaplastic and squamous cell populations. Cytogenetic analysis demonstrated that the lung metastases were derived from a specific subpopulation of cancer cells present in the original AT6 primary tumor. Immunohistochemical studies demonstrated that only the area of lung metastases displaying squamous morphology were positive for E-cadherin. In contrast, the anaplastic areas of the lung metastases and the metastases in other organs were E-cadherin negative. By the first passage of the AT6 tumor only the anaplastic cells were present and no detectable E-cadherin mRNA or protein was found in the primary tumor and metastatic deposits. These results suggest that a decreased expression of E-cadherin is associated with the progression of prostatic cancer.
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PMID:Decreased expression of E-cadherin in the progression of rat prostatic cancer. 158 9

The expression of human E-cadherin in normal tissues and in benign and malignant tumors of female genital organs was examined immunohistochemically with a monoclonal antibody, HECD-1, specific for human E-cadherin. The normal tissues included the ovary, fallopian tube, uterine endometrium, uterine cervix, and vagina. E-cadherin was detected clearly in the cell-to-cell boundaries of both normal glandular and squamous epithelia obtained from those tissues. The tumor tissues consisted of 9 ovarian, 7 endometrial, and 4 cervical adenocarcinomas, 12 squamous cell carcinomas of the cervix, including 3 cervical intraepithelial neoplasms, and 5 mesenchymal tumors. E-cadherin also was detected in the cell-to-cell borders of all the epithelial tumors tested, with some reactivity in the cytoplasm of malignant cells, whereas mesenchymal tumors showed no expression. It is noteworthy that poorly differentiated areas of both the adenocarcinomas and squamous cell carcinomas showed less expression of E-cadherin. No difference in the expression of E-cadherin between the primary and metastatic lesions was detected in 10 sets of malignant tumors. E-cadherin may be an important factor among a variety of biologic events that occur during the process of metastasis. However, further studies are needed to clarify this.
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PMID:Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs. 161 30

E-cadherin (E-CD), a Ca(2+)-dependent adhesion molecule, plays a major role in the maintenance of intercellular junctions in normal epithelial cells in most organs. The expression of E-CD in human carcinoma samples (esophagus, stomach, and breast) was investigated using immunohistochemical staining, which was performed on surgical specimens using a monoclonal antibody for human E-CD. E-cadherin was strongly expressed in all normal epithelium examined. However E-CD expression in primary tumors of esophagus (11 of 15: 73%), stomach (5 of 20: 25%), and breast (9 of 20: 45%) was reduced, and 68% of these (esophagus: 8 of 11, stomach: 4 of 5, breast: 5 of 9) displayed heterogeneous E-CD expression. In some tumor cells with reduced E-CD expression, E-CD molecules were located in the cell cytoplasm. These results indicate that there are human cancer cells in which E-CD-related intercellular adhesion is impaired.
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PMID:Expression of immunoreactive E-cadherin adhesion molecules in human cancers. 171 20


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