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The role of VEGF isoforms in tumor angiogenesis
Author(s) -
Finkelstein Eric B,
D’Amore Patricia A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a217-d
Subject(s) - angiogenesis , lewis lung carcinoma , gene isoform , vascular endothelial growth factor , genetically modified mouse , hif1a , biology , neovascularization , endocrinology , tumor progression , medicine , extracellular matrix , cancer research , transgene , chemistry , cancer , vegf receptors , microbiology and biotechnology , metastasis , gene , biochemistry
Purpose Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis. In mouse, alternative splicing of a single gene gives rise to three VEGF isoforms with 120, 164 and 188 amino acids. All isoforms are secreted from producing cells, but are either freely diffusible (VEGF120) or remain bound to the cell surface and extracellular matrix (VEGF188); VEGF164 has intermediate characteristics. Results from the generation of isoform‐specific mice indicate distinct roles in vascular development. We have begun to explore the role of VEGF isoforms in tumor angiogenesis. Methods Mice that express only VEGF188 were bred with RipTAg transgenic animals that spontaneously form tumors in their pancreatic islets. Tumor burden was compared to that of RipTAg animals wildtype (wt) for VEGF isoforms. In a second model, Lewis lung carcinoma (LLC) cells were implanted subcutaneously into wt mice or mice expressing only VEGF164 or VEGF188. This model, tests the role of stroma‐derived VEGF in tumor angiogenesis. Tumors were measured and the animals sacrificed 15 days post injection. Results RipTag animals expressing VEGF188 alone displayed a 74% reduction in tumor burden compared to those wt for VEGF isoforms, despite a similar tumor number (wt: 7.1 +/− 2.9; 188/188: 5.1 +/− 2.9). The volume of individual tumors was also smaller for 188/188 (9.5 mm 3 +/− 16.3) than wt (2.3 mm 3 +/− 3.8). Initial results of LLC indicate that mice with a single VEGF isoform (164 or 188) have a reduced ability to support tumor growth, compared to wt mice. We conclude that VEGF isoforms have differential abilities to support tumor growth, which may indicate distinct capacities to promote tumor angiogenesis. Funded by NRSA CA105734, PO1 CA4554