Enhancement of angiogenesis, tumor growth, and metastasis by transfection of vascular endothelial growth factor into LoVo human colon cancer cell line

The expression of vascular endothelial growth factor (VEGF), a highly poten t angiogenic molecule, is thought to be correlated with the development of colon cancer; however, direct evidence for a role of VEGF in metastasis is lacking. This study nas designed to more directly establish the role of VEG F in the growth and metastasis of human colon cancer using a genetically en gineered cancer cell line. A stable VEGF gene-transfected human colon cance r cell line, LoVo, was made by genetic manipulation using eukaryotic expres sion constructs designed to express the complete VEGF(121) cDNA in the sens e orientation. Transfected clones were screened for VEGF(121) mRNA expressi on by Northern blot analysis and for VEGF(121) protein expression by Wester n blot analysis, Consequently, we obtained S17 cells that expressed a high level of both VEGF mRNA and VEGF protein. A vector-transfected clone (V7 ce ll) was used as a control, The experiment with the dorsal air sec method re vealed that S17 cells elicited a stronger directional outgrowth of capillar ies than V7 cells, S17 cells formed faster-growing tumors than did V7 cells when xenografted s.c. into nude mice, although there was no significant di fference in their in vitro proliferation, Tumors derived from S17 cells had more vascularity, as assessed by counting capillary vessels after staining with factor VIII? than did tumors derived from V7 cells (P < 0.05), with r egard to the metastatic potential, S17 cells exhibited a higher capacity fo r both hepatic metastasis after the splenic portal inoculation and peritone al dissemination after i.p. injection than did VF cells. However, S17 cells show ed no apparent metastasis, despite their rapid growth after orthotopi c implantation. In conclusion, the present study shelved clearly that VEGF plays an important role in cancer growth due to stimulation of angiogenesis by accelerating cell growth after reaching the target organs.