INVOLVEMENT OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AND UROKINASE-TYPE PLASMINOGEN-ACTIVATOR RECEPTOR IN MICROVESSEL INVASION IN HUMAN COLORECTAL CANCERS

To evaluate the association among known angiogenic growth factors or f actors related to the plasminogen activation system and clinicopatholo gical factors in patients with colorectal cancer, we examined the expr ession of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha), ur okinase-type plasminogen activator (u-PA), u-PA receptor (uPA-R) and p lasminogen activator inhibitor-1 (PAI-1) in clinical specimens of colo rectal cancers by Northern blot analysis. In comparison with the expre ssion of these angiogenesis-related genes in 7 paired samples of color ectal cancers and the adjacent normal mucosa, VEGF mRNA level was sign ificantly higher in the cancer tissues than in the adjacent normal muc osa (p < 0.05). We analyzed expression of these genes in 44 cases of p rimary colorectal cancers. Among the 3 angiogenic growth factors we ex amined, VEGF mRNA expression was significantly higher in the cancer ti ssues with blood vessel invasion or with lymphatic vessel invasion tha n in those without, respectively (p < 0.05), On the other hand, u-PA-R mRNA expression was significantly higher in the cancers with blood ve ssel invasion than in those without (p < 0.05). In addition, there was a correlation between the expression levels of VEGF and u-PA-R mRNA i n the cancer tissues we have examined. Using immunohistochemistry, str ong staining of VEGF or u-PA-R was observed in the cancer cells invadi ng the microvessels. Our findings suggest that malignant transformatio n might accompany the upregulation of VEGF expression in colorectal ca ncers and that VEGF and u-PA-R might contribute cooperatively to incre ase angiogenesis around the tumor as well as the metastasis via microv essels, (C) 1998 Wiley-Liss, Inc.