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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first step of invasion and metastasis is the detachment of cancer cells in the primary tumor, which is mainly controlled by the function in the adherens junction, consisting of E-cadherin associated proteins (E-cadherin, alpha- and beta-catenins, vinculin, alpha-actinin, and actin). The cell-to-cell aggregation activity and the expressions of E-cadherin, and alpha- and beta-catenin mRNAs in Ishikawa cells of well-differentiated endometrial cancer were significantly suppressed by estrogen. These suppressions were reversed by progesterone, medroxyprogesterone acetate (MPA) and danazol. Proteins in the adherens junction appeared to be expressed intact and to be functional in Ishikawa cells. Persistent estrogen predominant milieu might contribute to the detachment of well-differentiated endometrial cancer cells, leading to spreading of those cells, while progestins and danazol protect estrogen-induced spreading of those cells.
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PMID:Progestins and danazol effect on cell-to-cell adhesion, and E-cadherin and alpha- and beta-catenin mRNA expressions. 863 63

Over the past 10 years it has become apparent that invasion and metastasis are extremely complex processes; neoplastic cells must escape from the primary tumor, degrade the extracellular matrix, migrate to distant sites, arrest in the capillaries, and migrate through the basement membrane and underlying connective tissue to the metastatic site. Therefore, tumor cells must exhibit considerable flexibility in their adhesive interactions, and this is reflected in a complex and dynamic expression pattern of cell adhesion molecules, proteases, protease inhibitors, motility factors, and growth factors. Despite the recent explosion of information regarding adhesion-related molecules, questions as to their possible roles in normal tissue architecture and as to how alterations in their expression or structure may be responsible for the progression from a single malignant cell to a lethal metastatic disease need further investigation. Moreover, efforts should be made to use the obtained knowledge to contribute to improvements in the clinical management of cancer. In this review the different classes of cell adhesion molecules and proteases are summarized, with special emphasis being placed on molecules that have been shown to correlate with invasion and metastasis. Furthermore, the role of E-cadherin in cell adhesion and invasive processes is discussed in more detail, since E-cadherin may be considered promising as a candidate among cell-adhesion-regulating molecules to be used as a biomarker for malignancy. We also elaborate on the role of the catenins, which associate with and are important for the functioning of E-cadherin.
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PMID:The role of cell adhesion molecules and proteases in tumor invasion and metastasis. 880 93

Recent molecular biology investigations have demonstrated that tumor progression and dissemination in bladder cancer is a highly complicated phenomenon, consisting of multiple distinct steps and regulated by a great number of different genes. Some of these genes involved in the specific steps of tumor progression and dissemination have been identified. Several oncogenes, e.g., the epithelial growth factor receptor (EGF-R), and tumor-suppressor genes, e.g., the p53 gene, have been found to correlate significantly with tumor progression. The decreased expression of cell-adhesion molecules such as E-cadherin appears to facilitate tumor-cell detachment in the primary tumor, whereas expression of the intercellular adhesion molecule (ICAM)-1 might be of relevance for cell attachment at the metastatic site. Tumor invasion through the basement membrane has been correlated with a decreased expression of laminin and elevated urinary levels of acidic fibroblast growth factor. Although the complex processes related to dissemination are far from being completely understood, the finding of differential expression of distinct genes appears to provide the first targets for therapeutic intervention.
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PMID:Molecular biology of dissemination in bladder cancer--laboratory findings and clinical significance. 880 98

Aberrant glycosylation expressed in glycosphingolipids and glycoproteins in tumor cells has been implicated as an essential mechanism in defining stage, direction, and fate of tumor progression. This general concept is supported by results from three lines of study: (a) Numerous clinicopathological studies have shown a clear correlation between aberrant glycosylation status of primary tumor and invasive/metastatic potential of human cancer as reflected by 5- or 10-year survival rates of patients. (b) Carbohydrates expressed in tumor cells are either adhesion molecules per se or modulate adhesion receptor function. Some are directly involved in cell adhesion. They are recognized by selectins or other carbohydrate-binding proteins or by complementary carbohydrates (through carbohydrate-carbohydrate interaction). N- or O-glycosylation of functionally important membrane components may alter tumor cell adhesion or motility in a direction that either promotes or inhibits invasion and metastasis. Examples of such receptors are E-cadherin, integrins, immunoglobulin family receptors (e.g., CD44), and lysosome-associated membrane protein. (c) Gangliosides and sphingolipids modulate transmembrane signaling essential for tumor cell growth, invasion, and metastasis. The transducer molecules susceptible to gangliosides and sphingolipids include integrin receptors, tyrosine kinase-linked growth factor receptors, protein kinase C, and G-protein-linked receptor affecting protein kinase A. Some glycosphingolipids (e.g., Gb3Cer, Le(y), ceramide, and sphingosine induce tumor cell differentiation and subsequent apoptosis. Shedded gangliosides may block immunogenicity of tumor cells, providing conditions favorable for "escape" from immunological suppression of tumor growth by the host. Various reagents that block carbohydrate-mediated tumor cell adhesion or block glycosylation processing have been shown to inhibit tumor cell metastasis. This provides the basis for further development of "anti-adhesion therapy." Ganglioside analogues and sphingolipid analogues that inhibit protein kinase C and receptor-associated tyrosine kinase have been applied for inhibition of metastasis. A crucial mechanism for inhibition of metastasis by these reagents may involve blocking of transmembrane signaling for expression of P- and E-selectin. This provides the basis for development of "ortho-signaling therapy."
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PMID:Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. 896 75

Reduced expression of E-cadherin has been associated with loss of differentiation and/or increased invasiveness and metastatic ability in several types of neoplasms. Rare studies on thyroid tumors have shown minimal or absent expression in undifferentiated carcinomas and a variable degree of immunoreactivity/mRNA expression in follicular and papillary carcinomas. We studied immunohistochemically 2 follicular adenomas, 8 follicular carcinomas, 18 papillary carcinomas and 3 poorly differentiated carcinomas to evaluate E-cadherin expression. In 7 papillary carcinomas, lymph node metastases were also studied. The E-cadherin gene was analysed in 27 tumors by PCR/SSCP followed, whenever appropriate, by DNA sequencing. LOH at the E-cadherin locus was assessed in 16 tumors. Reduced and heterogeneous expression of E-cadherin was found in primary and metastatic papillary carcinomas, whereas follicular carcinomas showed moderate to strong homogeneous immunoreactivity, and poorly differentiated carcinomas showed no or very faint immunoreactivity. The only case harbouring a (missense type) mutation of the E-cadherin gene was a papillary carcinoma exhibiting immunoreactivity in the primary tumor as well as in metastasis. LOH was found in a follicular adenoma and in a poorly differentiated carcinoma without evidence of mutation in the remaining allele. Our results show that irreversible alterations (allele loss or mutation) of the E-cadherin gene are infrequent in thyroid tumors. The reduced and heterogeneous expression of E-cadherin in thyroid carcinomas, particularly of the papillary histotype, appears to reflect transcriptional regulation or post-transcriptional modulation rather than structural abnormalities.
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PMID:E-cadherin gene alterations are rare events in thyroid tumors. 898 87

Loss of homotypic cell adhesion is an important prerequisite for invasion and metastasis of epithelial tumor cells. The function of E-cadherin, which mediates epithelial cell-cell adhesion, is regulated by a complex of proteins bound to its cytoplasmic tail, including a-, b-, g-catenins and plakoglobin (PG). The present study was designed to assess whether downregulation of plakoglobin expression occurs in human non-small cell lung carcinomas (NSCLC) and whether this change is associated with an unfavorable prognosis. Using immunohistochemistry with monoclonal antibody (mAb) PG 5.1 to PG, absence or severely reduced expression of PG (i.e., less than 30% of positive tumor cells) was observed in 39 of 97 patients (40.2%) with completely resected primary NSCLC (stages T1-3, N1-2, M0). There was no significant correlation to any of the analyzed clinicopathologic factors such as histologic type, grade or size of the primary tumor, and lymph node involvement. After a median observation period of 39 months (12-56 mo.), univariate Kaplan-Meier analysis showed that patients with PG-deficient primaries tended to have a shortened disease-free survival (p = 0.06). This correlation was statistically significant in patients with adenocarcinomas (p = 0.010), locally restricted primary tumors (pT1/2, p = 0.017), and negative lymph nodes (pN0, p = 0.036). Analysis of the overall survival in these subgroups also revealed significant associations between deficient PG expression and poor outcome (p < or = 0.036). Multivariate analysis was performed for the largest subgroup of patients with pT1/2 tumors (n = 66), demonstrating that PG expression was a strong, independent predictor of tumor relapse (p = 0.002). Thus, deficient expression of PG is a frequent, early event in the progression of NSCLC, which appears to predict an unfavorable prognosis in patients at earlier stages of their disease.
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PMID:[Expression of plakoglobin in bronchial carcinomas: incidence and significance for disease outcome]. 910 95

E-cadherin is a calcium-dependent, epithelial cell adhesion molecule whose reduced expression has been associated with tumor dedifferentiation and increased lymph node metastasis in clinical studies involving several carcinomas. In this study, 111 patients who had previously undergone complete resection and systematic mediastinal lymph node dissection for non-small cell lung cancer (NSCLC) were studied retrospectively. In the primary tumor, as well as in the lymph node metastases, E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1; Takara, Otsu, Japan). There was a significant inverse correlation between E-cadherin expression and lymph node stage (Pearson correlation coefficient -0.52, p = 0.0001) as well as tumor differentiation (Pearson correlation coefficient -0.27, p = 0.005). Moreover, Kaplan and Meier survival estimates showed a significant correlation between E-cadherin expression and patient survival in log rank testing (p = 0.006). In the patient group with the highest proportion of E-cadherin positive tumor cells, 60% of the patients were still estimated to be alive at 36 mo, versus 32% of the patients in the group classified as showing negative E-cadherin expression. Our findings provide clinical evidence that reduced E-cadherin expression is associated with tumor dedifferentiation, increased lymphogenous metastasis and poor survival. It seems therefore that E-cadherin expression might be an important prognostic factor in NSCLC.
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PMID:Reduced E-cadherin expression is associated with increased lymph node metastasis and unfavorable prognosis in non-small cell lung cancer. 956 56

Although impaired expression of E-cadherin (E-cad) is frequently observed in tumors with aggressive histopathologic characteristics, the correlation between alpha-catenin (alpha-cat) expression and the clinicopathologic features of early gastric cancer have not been fully examined. In this study, we evaluated the expression of E-cad and alpha-cat by early gastric carcinomas, and examined the relationships between this expression and various clinicopathologic characteristics. A total of 69 specimens obtained from surgery were studied by immunohistochemistry. Reduced expression of E-cad and alpha-cat were found in 53.6% and 65.2% of the tumors, respectively, and a significant correlation was observed between the decreased expression of E-cad or alpha-cat and tumor histology, the quantity of stroma, and the infiltration pattern of the tumor. The reduced expression of alpha-cat correlated more strongly with these features than E-cadherin expression. Furthermore, alpha-cat expression was also related to the lymph node metastasis of tumors. The expression of E-cad or alpha-cat in the primary tumor was consistent with the expression of tumor cells that invaded the lymphatic vessels, but discordant with staining in the metastasized lymph nodes. In some cases, as the tumor invaded deeper, the expression of E-cad or alpha-cat changed from preserved to reduced. Our observations suggest that the reduced expression of E-cad or alpha-cat may be involved in the initial steps leading to the invasion and metastasis of early gastric cancer.
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PMID:The expression of cadherin-catenin complex in association with the clinicopathologic features of early gastric cancer. 968 6

Distant metastasis is the most predominant clinical problem in renal cell carcinoma. The first step of metastasis is detachment of tumor cells from the primary tumor and subsequent access to the circulation e.g. to lymph or blood vessels. Conceptually, detachment of tumor cells may be facilitated by loss of molecules that provide adhesion of normal cells, such as the cadherins. It has in fact been demonstrated that loss of E-cadherin is associated with invasion and metastasis in animal models and with an unfavorable prognosis in cancer patients. Four major cadherins have been demonstrated in normal kidney and renal cell carcinoma: N-cadherin, E-cadherin, ksp-cadherin, and cadherin 6. The particular role of each of these cadherins in pathogenesis of renal cell carcinoma is not completely understood at present.
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PMID:Cadherins in renal cell carcinoma. 1036 32

This study examined the relationship between the expression of E-cadherin or beta-catenin in murine adenocarcinomas and their hematogenous metastatic propensity, assessed by both spontaneous and artificial lung metastasis. Seven different carcinomas, syngeneic to C3Hf/Kam mice were used: 4 mammary carcinomas (MCa-4, MCa-29, MCa-35, and MCa-K), ovarian carcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa-SG. These tumors vary widely in their ability to spontaneously metastasize to the lung (from 0 to 100% metastatic incidence), and their cells greatly differ in their ability to form artificial lung nodules when injected i.v. Primary tumors in the leg were assessed for E-cadherin and beta-catenin expression by western blotting. The expression of both proteins showed wide variation among the tumors; however, the expression of E-cadherin correlated well with that of beta-catenin. There was significant inverse correlation between the expression of E-cadherin, as well as beta-catenin, and the incidence of both spontaneous and artificial lung metastases from these tumors. Spontaneous metastases of highly metastatic HCa-I and moderately metastatic MCa-35 were significantly lower in E-cadherin and beta-catenin expression than their corresponding primary tumors were. Thus, the propensity of murine carcinomas for hematogenous spread is highly related to E-cadherin and beta-catenin levels in primary tumors. The inverse correlation between the expression of these molecules and spontaneous and artificial metastases implies that tumor cells with low E-cadherin and beta-catenin content have increased ability to enter the vascular circulation at the primary tumor site and to colonize distant tissues.
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PMID:Low E-cadherin and beta-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas. 1041 Nov 10


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