c-fos-induced growth factor/vascular endothelial growth factor D induces angiogenesis in vivo and in vitro.
c-fos-induced growth factor/vascular endothelial growth factor D (Figf/Vegf-D) is a secreted factor of the VEGF family that binds to the vessel and lymphatic receptors VEGFR-2 and VEGFR-3. Here we report that Figf/Vegf-D is a potent angiogenic factor in rabbit cornea in vivo in a dose-dependent manner. In vitro Figf/Vegf-D induces tyrosine phosphorylation of VEGFR-2 and VEGFR-3 in primary human umbilical cord vein endothelial cells (HUVECs) and in an immortal cell line derived from Kaposi's sarcoma lesion (KS-IMM). The treatment of HUVECs with Figf/Vegf-D induces dose-dependent cell growth. Figf/VEGF-D also induces HUVEC elongation and branching to form an extensive network of capillary-like cords in three-dimensional matrix. In KS-IMM cells Figf/Vegf-D treatment results in dose-dependent mitogenic and motogenic activities. Taken together with the previous observations that Figf/Vegf-D expression is under the control of the nuclear oncogene c-fos, our data uncover a link between a nuclear oncogene and angiogenesis, suggesting that Figf/Vegf-D may play a critical role in tumor cell growth and invasion.
Marconcini
L
L
Dipartimento di Biologia Molecolare Università degli Studi di Siena, via Fiorentina 1-53100 Siena, Italy.
Marchio
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Morbidelli
L
L
Cartocci
E
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Albini
A
A
Ziche
M
M
Bussolino
F
F
Oliviero
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D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D003315:Cornea / Q000098:blood supply; D006224:Cricetinae; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000494:pharmacology*; D011817:Rabbits; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D014443:Tyrosine / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3
D016228:Endothelial Growth Factors; D016760:Proto-Oncogene Proteins c-fos; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D042643:Vascular Endothelial Growth Factor D; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040321:Vascular Endothelial Growth Factor Receptor-3