Mechanisms responsible for peritoneal metastasis and lymph node metastasis in scirrhous gastric carcinoma

硬质胃癌腹膜转移和淋巴结转移的机制

基本信息

批准号：
13470260
负责人：
HIRAKAWA Kosei
金额：
$ 3.65万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

项目摘要

Prognosis of advanced stage gastric carcinoma remains poor because of the frequent incidence of metastasis. We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. Peritoneal-seeding cell line, OCUM-2MD3, was established from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both α2β1 and α3β1 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the adhesion ability of OCUM-2MD3 cells to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination g … More iven YIGSR sequence intraperitoneally was obviously longer than that of untreated mice. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM. The peritoneal injection of adhesion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients.We transfected ICAM-1 genes into gastric cancer cell line, 2MLN, and analyzed the effect on the lymph node metastasis of the transduction of ICAM-1 in vitro and in vivo. Lymph node metastases caused by 2MLN/ICAM cells were recognized as being fewer in number and smaller, while many lymph node metastases caused by 2MLN cells were recognized. These findings indicate that ICAM-1 gene might be a tumor suppressor gene that is important for lymph node metastasis, and that ICAM-1 gene transduction could prove to be an effective gene therapy for lymph node metastasis of gastric cancer. Less

由于转移的频繁发生，晚期胃癌的预后仍然较差。我们检查了粘附多肽对从不良接种的胃癌细胞系 OCUM-2MD3 的粘附和侵袭性的影响。人硬质胃癌细胞系 OCUM-2M α2β1 和 α3β1 整合素表达在 OCUM-2MD3 上显着增加。与OCUM-2M细胞相比，OCUM-2MD3细胞对细胞外基质（ECM）的粘附能力也显着高于OCUM-2M细胞，粘附多肽、YIGSR和RGD显着抑制OCUM-2MD3细胞的粘附。 2MD3细胞与间皮下ECM的结合，同时不抑制OCUM-2M细胞和两种分化良好的人胃细胞系的粘附性， MKN-28和MKN-74也显着抑制了OCUM-2MD3细胞的侵袭性，腹膜内转移YIGSR序列的裸鼠的存活时间明显长于未处理的小鼠。似乎可以阻断 OCUM-2MD3 细胞上表达的整合素与间皮下 ECM 的结合。腹腔注射粘附多肽可能是对抗硬质胃癌播散的新疗法，并且可能有助于预防高危患者的播散。我们将ICAM-1基因转染到胃癌细胞系2MLN中，并分析了体外和体内转导ICAM-1对淋巴结转移的影响 2MLN/ICAM细胞引起的淋巴结转移数量较少。且更小，同时识别出许多由2MLN细胞引起的淋巴结转移。这些发现表明ICAM-1基因可能是对淋巴结转移很重要的抑癌基因，并且ICAM-1基因转导可能被证明是有效的。胃癌淋巴结转移的基因治疗较少。