Role of VLA-3 integrin in adhesion of cancer cells to peritoneum.

胃癌细胞与腹膜的黏附是腹膜扩散的第一步。已有研究表明，各种细胞黏附分子，如整合素，在黏附过程中起着关键作用。临床标本的免疫组织化学分析显示，vla-3(α3β1)整合素的表达与胃癌腹膜转移潜能呈正相关。这一观察结果提示VLA-3整合素可能在胃癌腹膜转移过程中发挥重要作用。在本研究中，我们进行了体外和体内实验，以评估VLA-3在癌细胞与腹膜黏附中的作用。将人α-3整合素基因导入K562白血病细胞，发现α-3整合素转基因细胞(K3-9细胞)与小鼠腹膜的黏附能力高于空白对照细胞(KR细胞)。此外，抗VLA-3的单抗部分抑制了四种人胃癌细胞系与腹膜的黏附。RT-PCR法检测VLA-3的高亲和力配体LN 5和LN 10/11的表达。在横隔膜和腹膜中检测到层粘连蛋白5和层粘连蛋白10/11的mRNA，提示层粘连蛋白家族的这些成员参与了VLA-3介导的癌细胞黏附。为了评价VLA-3整合素在体内腹膜扩散中的作用，将K3-9和KR细胞接种到SCID小鼠的腹膜内，观察到K3-9细胞腹腔接种3周后腹膜和横隔部肿瘤的形成，这些结果有力地表明VLA-3整合素介导了癌细胞在腹膜上的初始附着，癌细胞上VLA-3的过表达促进了腹膜内肿瘤的生长。

The adhesion of gastric cancer cells to peritoneum is a key step in the first process of peritoneal dissemination. It has been shown that various cell adhesion molecules, such as integrins, play critical roles in the adhesion. Immunohistochemical analysis of clinical specimens of gastric cancer revealed that VLA-3 (α3β1 integrin) expression is positively correlated with the peritoneal metastatic potential. This observation suggests that VLA-3 integrin may play an important role in the process of peritoneal metastasis of gastric cancer.In this study, we conducted in vitro and in vivo experiments to assess the role of VLA-3 in the adhesion of cancer cells to peritoneum. The cDNA to human α3 integrins were introduced into K562 leukemic cells, The α3 integrin-transfected cells (K3-9 cells) were found to have higher capacity in the adhesion to mouse peritoneum than the mock transfected cells (KR cells). Furthermore, the adhesion of four human gastric carcinoma cell lines to the peritoneum was partially inhibited by a monoclonal antibody against VLA-3. The expression of laminin 5 and laminin 10/11, high affinity ligands for VLA-3, was examined by the RT-PCR method. The mRNA for laminin 5 and laminin 10/11 was detected in diaphragm and peritoneum, suggesting that these members of the laminin family are involved in the VLA-3-mediated adhesion of cancer cells. In order to evaluate the contribution of VLA-3 integrin in peritoneal dissemination in vivo, K3-9 and KR cells were inoculated into the abdominal cavity of SCID mice, The formation of tumor associated with the peritoneum and diaphragm was observed three weeks after i. p. inoculation of K3-9 cells.These results strongly suggest that VLA-3 integrin mediates the initial attachment of cancer cells to peritoneum and that the overexpression of VLA-3 on cancer cells promotes the intraperitoneal tumor growth.