Interaction of proinflammatory cytokines and growth factors in gastric carcinogenesis

我们已经报道，高胃泌素血症和IL-1β的产生增加可能是幽门螺杆菌相关性肥大折叠性胃炎小凹增生的原因，胃泌素诱导胃粘膜中肝素结合的表皮生长因子(HB-EGF)和双调节素的产生。本研究的目的是阐明促炎细胞因子和生长因子在胃癌发生中的作用。胃泌素通过激活核因子kappaB与IL-1β协同作用诱导IL-8表达。皱褶型胃炎患者胃粘膜8-羟基脱氧鸟苷生成增加，抑癌基因启动子区高甲基化。HB-EGF与CD9在胃癌中的表达呈正相关。抗CD9抗体通过p46Shc亚型酪氨酸磷酸化抑制细胞增殖，诱导胃癌细胞凋亡。胃泌素、促炎细胞因子和生长因子被证明与胃癌的发生有关。

We have reported that hypergastrinemia and increased IL-1beta production may contribute to foveolar hyperplasia in Helicobacter pylori-associated enlarged fold gastritis and that gastrin induces heparin binding epidermal growth factor-like growth factor(HB-EGF) and amphiregulin production in the gastric mucosa. The purpose of the present study was to clarify the roles of proinflammatory cytokines and growth factors in gastric carcinogenesis. Gastrin induced IL-8 expression through activation of nuclear factor kappaB in cooperation with IL-1beta. Increased 8-hydroxydeoxyguanosine production and hypermethylation in the region of promoter of tumor suppressor genes were observed in the gastric mucosa of patients with enlarged fold gastritis. HB-EGF expression was associated with CD9 expression in gastric cancer. Anti-CD9 antibody inhibited cell proliferation and induced apoptosis in gastric cancer cells through tyrosine phosphorylation of the p46 Shc isoform. Gastrin and proinflammatory cytokines and growth factors were shown to be involved in gastric carcinogenessis.