Takahashi Y, Cleary K R, Mai M, Kitadai Y, Bucana C D, Ellis L M
Departments of Cell Biology, Surgical Oncology, and Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 1996 Oct;2(10):1679-84.
Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by host and/or tumor cells. The role of angiogenesis and angiogenic factor expression in intestinal- and diffuse-type gastric cancer are undefined. Archival specimens of 51 intestinal-type and 38 diffuse-type human gastric carcinomas were examined for tumor vessel counts, angiogenic factor expression, and the presence or absence of angiogenic factor receptors on tumor endothelium using antibodies against vascular endothelial growth factor (VEGF) and its receptors (KDR and flt-1), basic fibroblast growth factor (bFGF) and its receptors (bek and flg), and factor VIII (endothelial cells). Vessel count and VEGF and bFGF expression were higher in intestinal-type than in diffuse-type gastric cancers (P = 0.01, P < 0.001, and P < 0.001, respectively). Similarly, vessel count and VEGF expression were higher in patients with liver metastasis than in patients with peritoneal dissemination (P = 0.003 and P = 0.01, respectively). Vessel count correlated with VEGF expression and the presence of endothelial KDR in intestinal-type gastric cancer (P = 0.003 and P = 0.02, respectively) but not diffuse-type gastric cancer. Vessel count, VEGF expression, and presence of endothelial KDR increased with increasing stage of disease in intestinal-type gastric cancer but not diffuse-type gastric cancer. The expression of bFGF and its receptors did not correlate with vessel count in either cancer type. These findings suggest that the pattern of metastasis in intestinal-type gastric cancer is angiogenesis dependent. The correlation of VEGF expression and its endothelial receptor with vessel count and stage of disease suggests that VEGF is at least one of the factors responsible for the induction of angiogenesis in intestinal-type gastric cancer.
血管生成对于肿瘤的生长和转移至关重要，并且依赖于宿主和/或肿瘤细胞产生血管生成因子。血管生成及血管生成因子表达在肠型和弥漫型胃癌中的作用尚不清楚。使用针对血管内皮生长因子（VEGF）及其受体（KDR和flt-1）、碱性成纤维细胞生长因子（bFGF）及其受体（bek和flg）以及因子VIII（内皮细胞）的抗体，对51例肠型和38例弥漫型人胃癌的存档标本进行肿瘤血管计数、血管生成因子表达以及肿瘤内皮上血管生成因子受体的有无检测。肠型胃癌的血管计数、VEGF和bFGF表达高于弥漫型胃癌（分别为P = 0.01、P < 0.001和P < 0.001）。同样，肝转移患者的血管计数和VEGF表达高于腹膜播散患者（分别为P = 0.003和P = 0.01）。在肠型胃癌中，血管计数与VEGF表达以及内皮KDR的存在相关（分别为P = 0.003和P = 0.02），但在弥漫型胃癌中无此相关性。在肠型胃癌中，血管计数、VEGF表达和内皮KDR的存在随疾病分期增加而增加，但在弥漫型胃癌中并非如此。在两种癌症类型中，bFGF及其受体的表达与血管计数均无相关性。这些发现表明，肠型胃癌的转移模式依赖于血管生成。VEGF表达及其内皮受体与血管计数和疾病分期的相关性表明，VEGF至少是肠型胃癌中诱导血管生成的因素之一。
