TISSUE-SPECIFIC EXPRESSION PATTERN OF VASCULAR ENDOTHELIAL GROWTH-FACTOR ISOFORMS IN THE MALIGNANT TRANSFORMATION OF LUNG AND COLON

Angiogenesis, a prerequisite far tumor growth and progression results from a shift in the equilibrium between angiogenic factors and angioge nic inhibitors. Vascular endothelial growth factor (VEGF) has been ide ntified as one of the most important factors mediating angiogenesis in physiological and pathological conditions. Through alternative splici ng, four isoforms of VEGF are formed, consisting of 206, 189, 165, and 121 amino acids, respectively. VEGF206 and VEGF189 differ from VEGF16 5 and VEGF121 in their bioavailability, with the longer forms being ma trix-bound and the shorter forms freely diffusible. To investigate the relative importance of the VEGF isoforms in neoplastic transformation , we studied the pattern of splice variant expression by reverse trans cription polymerase chain reaction (RT-PCR) in 18 lung and 11 colonic carcinomas and their corresponding normal tissues, respectively. The f indings showed a significant upregulation of VEGF in both carcinomas, with VEGF165 and VEGF121 being the predominant forms; VEGF189 was sign ificantly expressed in normal lung hut not colon; and VEGF206 was not detected in any specimen. The findings indicate that during malignant progression, an angiogenic switch favoring the shorter diffusible isof orms is likely to confer on the tumor a growth advantage. From the dif ferential expression of VEGF isoforms in normal lung and colonic tissu es, different functional roles of the splice variants is suggested. In particular, VEGF189 may be important for the maintenance of the vascu lar integrity of the lung. Copyright (C) 1998 by W.B. Saunders Company .