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Vol. 19, Issue 5, 2278-2288, May 2008

This Article Full Text Full Text (PDF) All Versions of this Article: E07-10-1068v1 19/5/2278    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yan, W. Articles by Shao, R. PubMed PubMed Citation Articles by Yan, W. Articles by Shao, R.

Distinct Angiogenic Mediators Are Required for Basic Fibroblast Growth Factor– and Vascular Endothelial Growth Factor–induced Angiogenesis: The Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis

Wei Yan^*, Brooke Bentley^*, and Rong Shao^*,

*Pioneer Valley Life Sciences Institute, Baystate Medical Center/University of Massachusetts at Amherst, Springfield, MA 01107; and Program of Molecular and Cellular Biology and Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA 01003

Submitted October 23, 2007; Revised February 21, 2008; Accepted February 28, 2008
Monitoring Editor: Mark Ginsberg

Signaling pathways engaged by angiogenic factors bFGF and VEGF in tumor angiogenesis are not fully understood. The current study identifies cytoplasmic tyrosine kinase c-Abl as a key factor differentially mediating bFGF- and VEGF-induced angiogenesis in microvascular endothelial cells. STI571, a c-Abl kinase inhibitor, only inhibited bFGF- but not VEGF-induced angiogenesis. bFGF induced membrane receptor cooperation between integrin β₃ and FGF receptor, and triggered a downstream cascade including FAK, c-Abl, and MAPK. This signaling pathway is different from one utilized by VEGF that includes integrin β₅, VEGF receptor-2, Src, FAK, and MAPK. Ectopic expression of wild-type c-Abl sensitized angiogenic response to bFGF, but kinase dead mutant c-Abl abolished this activity. Furthermore, the wild-type c-Abl enhanced angiogenesis in both Matrigel implantation and tumor xenograft models. These data provide novel insights into c-Abl's differential functions in mediating bFGF- and VEGF-induced angiogenesis.

Address correspondence to: Rong Shao (rong.shao{at}bhs.org)