Vascular endothelial growth factor C induces angiogenesis in vivo

Vascular endothelial growth factor C induces angiogenesis in vivo

^*Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; ^‡Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115; ^§Molecular/Cancer Biology Laboratory, Haartman Institute, PL 21, University of Helsinki, 00014 Helsinki, Finland; and ^¶Department of Medical and Physiological Chemistry, Biomedical Center, Box 575, S-751 23 Uppsala, Sweden

Communicated by George Klein, Karolinska Institutet, Stockholm, Sweden (received for review June 1, 1998)

Abstract

Vascular endothelial growth factor C (VEGF-C) recently has been described to be a relatively specific growth factor for the lymphatic vascular system. Here we report that ectopic application of recombinant VEGF-C also has potent angiogenic effects in vivo. VEGF-C is sufficiently potent to stimulate neovascularization from limbal vessels in the mouse cornea. Similar to VEGF, the angiogenic response of corneas induced by VEGF-C is intensive, with a high density of new capillaries. However, the outgrowth of microvessels stimulated by VEGF-C was significantly longer than that induced by VEGF. In the developing embryo, VEGF-C was able to induce branch sprouts from the established blood vessels. VEGF-C also induced an elongated, spindle-like cell shape change and actin reorganization in both VEGF receptor (VEGFR)-2 and VEGFR-3-overexpressing endothelial cells, but not in VEGFR-1-expressing cells. Further, both VEGFR-2 and VEGFR-3 could mediate proliferative and chemotactic responses in endothelial cells on VEGF-C stimulation. Thus, VEGF-C may regulate physiological angiogenesis and participate in the development and progression of angiogenic diseases in addition to lymphangiogenesis.

Footnotes

↵ † To whom reprint requests should be addressed. e-mail: yihai.cao{at}mtc.ki.se.
ABBREVIATIONS:

VEGF,

vascular endothelial growth factor;

VEGFR,

VEGF receptor;

PlGF,

placenta growth factor;

FGF,

fibroblast growth factor;

PAE cells,

porcine aortic endothelial cells;

FCS,

fetal calf serum;

CAM,

chorioallantoic membrane