Novel target therapy for the HGF/cMET axis and HB-EGF in gastric cancer

顽固性胃癌常发展为腹膜癌伴恶性腹水。我们研究了HGF/MET轴在硬化癌腹膜癌变中的作用。裸小鼠腹腔注射后，Scirrhous细胞系产生腹膜癌变伴大量腹水。外源性HGF可刺激其体外增殖。MET-TKIs可抑制hgf刺激的硬核细胞增殖。此外，MET-TKIs延长了由硬膜细胞形成的肿瘤小鼠的存活时间。在临床标本中，硬化癌的间质成纤维细胞明显产生HGF。我们的研究结果强烈提示，旁分泌hgf诱导的met介导的信号通路激活在硬结性胃癌腹膜癌的发病机制中起重要作用。因此，即使没有MET扩增，MET信号通路也可能是胃癌腹膜癌病的潜在治疗靶点。

Scirrhous gastric cancer frequently develops into peritoneal carcinomatosis with malignant ascites. We investigated the role of the HGF/MET axis in peritoneal carcinomatosis in scirrhous cancer. Scirrhous cell lines produced peritoneal carcinomatosis with massive ascites after intraperitoneal injection in nude mice. Their proliferation was stimulated by exogenous HGF in vitro. MET-TKIs inhibited HGF-stimulated proliferation of scirrhous cells. Furthermore, MET-TKIs prolonged the survival of mice bearing established tumors by scirrhous cells. In clinical specimens, HGF was markedly produced by stromal fibroblasts in scirrous cancer. Our results strongly suggest that paracrine HGF-induced activation of MET-mediated signaling pathways plays an important role in the pathogenesis of peritoneal carcinomatosis in scirrhous gastric cancer.Thus, MET signaling pathway may be a potential therapeutic target for peritoneal carcinomatosis of gastric cancer, even without MET amplification.