PMID: 11912163Mar 26, 2002Paper

Vascular endothelial growth factor isoform expression as a determinant of blood vessel patterning in human melanoma xenografts

Cancer Research
Joanne L YuR S Kerbel

Abstract

Vascular endothelial growth factor (VEGF) occurs in at least five different isoforms because of alternative splicing of the gene. To investigate the roles of different VEGF isoforms in tumor blood vessel formation and tumorigenicity, the three major isoforms (VEGF(121), VEGF(165), and VEGF(189)) were overexpressed in an early-stage human melanoma cell line (WM1341B), which is VEGF-negative and nontumorigenic in immunodeficient mice. Although overexpression of VEGF(121) and VEGF(165) resulted in aggressive tumor growth, WM1341B cells transfected with VEGF(189) remained nontumorigenic and dormant on injection. Although tumor growth rate depended on the level and not the isoform of VEGF expressed, striking isoform-specific differences in vascular patterning were associated with VEGF(121)- versus VEGF(165)-dependent tumorigenic conversion of human melanoma. Thus, tumors overexpressing VEGF(165) generated dense, highly heterogeneous vessel networks that were distinctly different from those of tumors expressing VEGF(121) (poorly vascularized and necrotic). Paradoxically, although VEGF(165) expression appears to result in the most effective tumor perfusion, it is the expression of VEGF(121) that is observed during human malignant mela...Continue Reading

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.