Clinicopathological significance of platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-β phosphorylation, and microvessel density in gastric cancer

Abstract

BackgroundAngiogenesis is important in the growth and metastasis of various kinds of solid tumors, including gastric cancers. The angiogenic process is triggered by several key growth factors, including vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF)-B, that are secreted by tumors. Our aim was to define: i) the expression pattern of VEGF-A and PDGF-B in tumor cells and the activation of PDGF receptor (PDGFR)-β tyrosine kinase in stromal cells of human gastric adenocarcinomas; and ii) the relationship between VEGF-A and PDGF-B expression and microvessel density (MVD), to determine if there is a rationale for a new therapeutic strategy.MethodsA series of 109 gastric adenocarcinoma cases that had undergone surgical resection was examined immunohistochemically using antibodies against VEGF-A, PDGF-B, and CD34, followed by further examination of PDGFR-β phosphorylation by immunoblotting analysis.ResultsMVD was higher in diffuse-type than intestinal-type cancers (p < 0.001). VEGF-A overexpression correlated to PDGF-B overexpression in both the intestinal-type (p < 0.005) and diffuse-type (p < 0.0001) groups, indicating that VEGF-A and PDGF-B are secreted simultaneously in the same tumor, and may thus play important roles together in angiogenesis. However, several differences between intestinal-type and diffuse-type cancers were observed. In the diffuse-type cancer group, higher MVD was related to the PDGF-B proportion (p < 0.05) and VEGF-A overexpression (p < 0.05), but not to PDGF-B overexpression or the VEGF-A proportion. On the other hand, in the intestinal-type cancer group, higher MVD was correlated to overexpression (p < 0.005), intensity (p < 0.05), and proportion (p < 0.05) of PDGF-B, but not of VEGF-A. In addition, phosphorylation of PDGFR-β was correlated with depth of cancer invasion at statistically significant level.ConclusionsOur results indicate that PDGF-B, which is involved in the maintenance of microvessels, plays a more important role in angiogenesis in intestinal-type gastric carcinomas than VEGF-A, which plays a key role mainly in the initiation of new blood vessel formation. In contrast, VEGF-A has a critical role for angiogenesis more in diffuse-type cancers, but less in those of intestinal type. Thus, a therapy targeting the PDGF-B signaling pathway could be effective for intestinal-type gastric carcinoma, whereas targeting VEGF-A or both VEGF-A and PDGF-B signaling pathways could be effective for diffuse-type gastric carcinomas.

Clinical significance of platelet-derived growth factor receptor-β gene expression in stage II/III gastric cancer with S-1 adjuvant chemotherapy

“…Kodama et al reported that PDGFR-β expression correlates with lymph node metastasis in gastric cancer (5). Suzuki et al showed that activation of PDGFR-β correlates with the depth of tumor invasion in gastric cancer (17), and Guo et al reported that PDGFR-β expression positively correlates with the depth of tumor invasion, lymph node metastasis and TNM stage in gastric cancer (16). By contrast, the expression levels of PDGFR-β mRNA were not associated with any clinicopathological features in the present study.…”

Expression of growth-regulated oncogene-1, hepatocyte growth factor, platelet-derived growth factor-AA and soluble E-selectin and their association with high-risk human papillomavirus infection in squamous cell carcinoma of the uterine cervix

“…Several studies have demonstrated that the upregulation of PDGF in numerous carcinomas is able to promote lymph node metastasis and tumor cell proliferation (26,27). Importantly, it can promote the formation of tumor blood vessels and lymph vessels (28,29). Therefore, PDGF may stimulate the growth and metastasis of tumors by angiogenesis and lymphangiogenesis.…”

Characteristics of B-lymphocytic infiltration in the peritumoral mucosa of the stomach in its cancer: Clinical and morphological aspects

“…Полагают, что основ-ные механизмы могут быть связаны с секрецией иммун-ными клетками цитокинов, хемокинов, факторов роста и протеаз [6,7,10], активацией ангиогенеза [4,5,11], с участием иммунных клеток в ремодуляции экстрацеллю-лярного матрикса, способствующих инвазии опухолевых клеток и метастазированию в отдаленные органы [4,6]. Роль В-лимфоцитов в опухолевой прогрессии остает-ся малоизученной.…”