Dynamics and Biological Significance of Vascular Growth Factors in Urogenital Cancers.

探讨肿瘤血管生成与血管生成因子在泌尿生殖道癌中的关系。血管内皮生长因子基因在半数以上的肾细胞癌中呈高表达。血管内皮生长因子基因的表达水平与肿瘤内微血管密度显著相关。免疫组织化学分析显示肾细胞癌胞浆内可见VEGF染色阳性。血管内皮生长因子基因在40%的BCAS中高表达。在蛋白水平上，膀胱癌细胞中VEGF呈明显阳性表达。两种肿瘤中血管内皮生长因子受体基因的表达与血管内皮生长因子基因的表达水平一致。我们研究了血管内皮生长因子相关基因(血管内皮生长因子A、B、C和D)在肾细胞癌中的表达，发现血管内皮生长因子A及其受体VEGFR-1和VEGFR-2在肾癌血管生成中起重要作用，而血管内皮生长因子受体B和血管内皮生长因子C在肾癌血管生成中的作用很小。肾癌患者组血清平均血管内皮生长因子水平高于健康对照组。术后血清血管内皮生长因子水平较术前明显下降。血清血管内皮生长因子水平与肿瘤体积、转移和分期显著相关。膀胱癌患者组血清平均血管内皮生长因子水平也高于健康对照组。因此，我们认为肾细胞癌和膀胱癌释放的血管内皮生长因子进入血液循环，血清中的血管内皮生长因子水平可以作为这些肿瘤恶性潜能的标志物，这些结果将为肾细胞癌和膀胱癌的诊断和治疗提供抗血管生成因子抗体的基础数据。

The relationship between tumor angiogenesis and angiogenic factors was evaluated in urogenital cancers. VEGF gene was overexpressed in more than a half of renal cell carcinoma (RCC). The expression level of VEGF genes was significantly correlated with the intratumoral microvessel density. An immunohistologic analysis revealed that cytoplasm of RCC appeared to be positive for the VEGF staining. VEGF gene was also overexpressed in 40% of BCas. At protein level, VEGF was apparently positive in bladder carcinoma cells. VEGF-receptor genes were expressed in concordance with the VEGF gene expression level in both tumors. Thus, angiogenesis in RCC and bladder cancer is suggested to be facilitated by a paracrine mechanism with VEGF and its receptors.We studied the expression of VEGF-relating genes (VEGF-A, B, C, and D) in RCCs and found that VEGF-A and the receptors, VEGFR-1 and VEGFR-2, play crucial roles in the angiogenesis of RCC while VEGF-B and VEGF-C do little.Based on the above results, we compared serum VEGF levels between cancer patients and healthy control subjects. The mean serum VEGF level was higher in the RCC patient group than in the healthy control group. Postoperative serum VEGF level apparently decreased as compared with the preoperative level. Serum VEGF level was significantly correlated with tumor volume, metastasis, and stage. The mean serum VEGF level was also higher in the bladder cancer patient group than in the healthy control group. Thus we suggest that RCC and bladder cancer release VEGF into the blood circulation and serum VEGF level would be a marker of malignant potential of these tumors.Taken together, these results would be useful as basic data for the development of antiangiogenic-factor antibody facilitating diagnosis and therapy of RCC and bladder cancer.