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Molecular and Cellular Biology, October 2000, p. 7282-7291, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Isoforms of Vascular Endothelial Growth Factor Act in a Coordinate Fashion To Recruit and Expand Tumor Vasculature

Jeremy Grunstein,1 Joseph J. Masbad,1 Reed Hickey,2 Frank Giordano,2 and Randall S. Johnson1,*

Department of Biology, University of California, San Diego, La Jolla, California,1 and Division of Cardiology, Yale University School of Medicine, New Haven, Connecticut2

Received 2 May 2000/Returned for modification 5 June 2000/Accepted 20 June 2000

Vascular endothelial growth factor (VEGF) is an essential regulator of vascularization. It is expressed as several splice variants; the major forms contain 120 amino acids, 164 amino acids, and 188 amino acids. We utilized transformed cells nullizygous for VEGF to specifically express each of these isoforms in isolation, in order to determine the role of each in tumorigenic neo-vascularization. We found that only the intermediate isoform, VEGF164, could fully rescue tumor growth; VEGF120 partially rescued tumor growth, and VEGF188 failed completely to rescue tumor expansion. Surprisingly, the vascular density of VEGF188 isoform-expressing tumors is significantly greater than that of wild-type VEGF cells and the other isoform-specific tumors. The failure of the hypervascular VEGF188-expressing tumors to grow may be due to inadequate perfusion of the massive number of microvessels in these tumors; three-dimensional imaging of the tumorigenic vasculature indicated little or no recruitment of the peripheral vasculature. This demonstrates that the VEGF isoforms perform unique functions which together enable tumorigenic vascularization.

* Corresponding author. Mailing address: Department of Biology, University of California, San Diego, Box 0366, Pacific Hall Rm. 1216, 9500 Gilman Dr., La Jolla, CA 92093-0366. Phone: (858) 822-0509. Fax: (858) 534-5831. E-mail: rjohnson{at}biomail.ucsd.edu.

Molecular and Cellular Biology, October 2000, p. 7282-7291, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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