Intratumoral VEGF and FGF1 administration alters tumor growth, vascular density, oxygenation, and expression of MCP-1 and interleukins.
The biological and physiological effects of exogenous FGF 1 and VEGF were measured using the KHT murine fibrosarcoma tumor model. Tumor-bearing C3H mice were treated intratumorally with either one or six daily doses of 6 microg/mouse FGF1, VEGF, or saline. Tumors were excised 24 hrs after the final injection. Compared to controls, only FGF1 treatment significantly increased tumor weight and size, and only in the 6 dose group. Both FGF1 and VEGF administration (6 dose) decreased tumor cell hypoxia as detected by EF5 uptake: 85% +/- 5% for FGF1 and 82% +/- 6% for VEGF versus 100% +/- 6% for controls. Decreased tumor cell EF5 staining, however, was not associated with changes in numbers of structural or angiogenic vessels. DiOC7 staining showed a slight decrease in perfused vessel numbers in tumors treated with daily VEGF. Intratumoral injections of FGF1 or VEGF also slightly decreased the tumor tissue chemokine MCP-1, interleukins (IL-1beta, IL-6, and IL-18) mRNA expression, and increased NFkappaB binding without altering Ap-1 binding of IkappaB protein expression. In summary, single pulse exposures of tumors to angiogenic factors had little or no effects on tumor growth or perfusion, while daily exposures stimulated tumor growth through improved tumor oxygenation. This improved vascular function occurs without an increase in vascular density.
Okunieff
Paul
P
Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Sun
Jianzhong
J
Fenton
Bruce
B
Liu
Weimin
W
Ding
Ivan
I
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000627:therapeutic use*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007378:Interleukins; D042461:Vascular Endothelial Growth Factor A; D016220:Fibroblast Growth Factor 1