Takahashi Y, Bucana C D, Akagi Y, Liu W, Cleary K R, Mai M, Ellis L M
Department of Surgical Oncology, Kanazawa University, Japan.
Clin Cancer Res. 1998 Feb;4(2):429-34.
We have previously shown that platelet-derived endothelial cell growth factor (PD-ECGF) is associated with angiogenesis of human colon cancer; this factor is expressed at high levels in vascular tumors that express low levels of vascular endothelial growth factor (VEGF). In these colon cancers, the major source of PD-ECGF is the infiltrating cells. In this study, we examined the role of PD-ECGF in the angiogenesis of human gastric cancer. Immunostaining for PD-ECGF was done on 93 gastric cancers previously stained for VEGF, basic fibroblast growth factor, and factor VIII-related antigen (specific for endothelial cells). To determine the cell type expressing PD-ECGF, double staining was done using antibodies to both PD-ECGF and CD68 (specific for macrophages). PD-ECGF was expressed more frequently in infiltrating cells (positive CD68 staining; 53.8%) than in tumor epithelium (9.7%; P < 0.0001). Infiltrating cells simultaneously stained positive for both PD-ECGF and CD68. An association between PD-ECGF expression in infiltrating cells, VEGF expression in tumor epithelium, and vessel count was observed in intestinal-type gastric cancer but not in diffuse-type gastric cancer. Vessel count was greater in tumors with high expression of both PD-ECGF and VEGF than in those with high expression of either factor alone (P = 0.002). Multiple angiogenic factors expressed by both tumor cells and infiltrating cells may play a role in the regulation of angiogenesis in intestinal-type gastric cancer.
我们之前已经表明，血小板衍生的内皮细胞生长因子（PD-ECGF）与人类结肠癌的血管生成有关；该因子在表达低水平血管内皮生长因子（VEGF）的血管肿瘤中高表达。在这些结肠癌中，PD-ECGF的主要来源是浸润细胞。在本研究中，我们检测了PD-ECGF在人类胃癌血管生成中的作用。对93例先前已用VEGF、碱性成纤维细胞生长因子和因子VIII相关抗原（内皮细胞特异性）染色的胃癌进行了PD-ECGF免疫染色。为了确定表达PD-ECGF的细胞类型，使用抗PD-ECGF和CD68（巨噬细胞特异性）抗体进行双重染色。PD-ECGF在浸润细胞（CD68染色阳性；53.8%）中的表达频率高于肿瘤上皮（9.7%；P<0.0001）。浸润细胞同时对PD-ECGF和CD68染色呈阳性。在肠型胃癌中观察到浸润细胞中PD-ECGF表达、肿瘤上皮中VEGF表达与血管计数之间存在关联，但在弥漫型胃癌中未观察到。与单独高表达任一因子的肿瘤相比，同时高表达PD-ECGF和VEGF的肿瘤血管计数更高（P=0.002）。肿瘤细胞和浸润细胞表达的多种血管生成因子可能在肠型胃癌血管生成的调节中发挥作用。
