Relationship between cell adhesion molecules expression and the biological behavior of gastric carcinoma

Abstract

analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 (P < 0.01, in all cases). COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma (P < 0.01), whereas E-cadherin and integrin β3 could not be independent indexes (P > 0.05, P > 0.05 respectively). CONCLUSION:The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis of gastric carcinoma, and they are highly correlated with each other. Therefore they may serve as important prognostic markers of gastric carcinoma. INTRODUCTIONGastric carcinoma is the most common malignant tumor of the digestive system. Two of the most important causes for the high mortality are invasion and metastasis. However, the mechanism of invasion and metastasis of gastric carcinoma is still not definitely clear at present [1] . Cell adhesion is one of the important steps in metastasis. Syndecan-1, E-cadherin and integrin β3 make up cell adhesion molecules (CAMs) and participate in the adhesion between the cell and the extracellular matrix [2] . Syndecan-1 is a set of transmembrane heparitin sulfate glycoproteins (HSPGS), which is present at the surface of most epithelia cells and take part in the adhesion between the cell and the extracellular matrix. The expression of syndecan-1 was augmented during epithelial regeneration and rearrangement in the stomach and other tissues [3,4] . E-cadherin is a calcium dependent intercellular Abstract AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS:Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 nontumor gastric mucosas. RESULTS:T h e e x p r e s s i o n s o f s y n d e c a n -1 a n d E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). In addition, the three protein expressions were correlated to the tumor growth pattern (P < 0.01, P < 0.01, and P < 0.05 respectively), but not correlated to tumor differentiation (P > 0.05, P > 0.05 and P > 0.05 respectively). Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 (P < 0.01 in all cases). Univariate

Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma.

“…Except positive direct relation with histological grading of cancers, no significant associations between syndecan-1 expression and clinicopathological parameters were revealed. A similar correlation with tumor differentiation was also seen in the squamous cell carcinoma of various locations e.g., of head and neck [16,17], and uterine cervix [18] as well as in adenocarcinomas including that of the stomach [19], large intestine [20], liver (both hepato-and cholangiocellular carcinomas) [21,22], kidney [23] and endometrium [24]. These proved the importance of epithelial syndecan-1 in maintaining differentiating phenotypes, not only in physiological conditions, but in a variety of neoplasms as well.…”

“…A flattened, cuboidal shape, typical of epithelial cells, was replaced by an elongated fusiform shape, which was accompanied by the ability to migrate in collagen gels as well as anchorage-independent growth [5]. It should be stressed that in many tumors mentioned above, negative syndecan-1 expression correlated with at least some of the unfavorable markers like more advanced stage, deeper level of infiltration, vascular invasion, lymph node, or distant metastasis [19][20][21][22][23][24][25]. An abnormal expression of syndecan-1 was also revealed in precursor lesions.…”

Caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous tissues and chronic non-atrophic gastritis

“…In this study, we have also found that gastric intestinal metaplasia as well as the cells at the base and neck of gastric pits within all fundic mucosal fragments showed caveolin-1 immuno-staining, suggesting a histogenetic derivation of these lesions from the transdifferentiation of chief cells or from a cryptic progenitor population at the base of fundic glands. [16] discovered a decreased E-cadherin expression was related to invasion and metastasis of gastric carcinoma. Utsunomiya, et al [15] A report from Zhou, et al also discovered that a decrease of E-cadherin or β-catenin or both could weaken cell-cell adhesion and resulted in cell dissipation that made cancer cell infiltration and metastasis easier.…”

“…In many malignant tumors, downexpression or destruction of E-cadherin and β-catenin is one of the changes that characterize an invasive phenotype. These genes are considered to be invasion/tumor suppressor genes, and partial or complete loss of E-cadherin and β-catenin expression is reported to be associated with poor prognosis in malignant tumors [11,[14][15][16][17] .…”

Modern concepts of factors for gastric cancer progression

“…Мутации CDH1 были выявлены в 40-83% спорадических случа-ев рака желудка диффузного типа, но отсутствовали или были редки при карциномах кишечного типа [29]. Снижение экспрес-сии Е-кадхерина было связано с низкой дифференцировкой опу-холи, более глубокой инвазией и снижением общей выживаемо-сти больных раком желудка [30,31].…”