Site-dependent angiogenic cytokine production in human tumor xenografts.
Tumor microenvironment plays a critical role in tumor growth, angiogenesis, and metastasis. Differences in site of tumor implantation result in differences in tumor growth, metastasis, as well as response to chemotherapy. We hypothesized that tumor-induced angiogenic growth factor production into the plasma will also be influenced by site of tumor implantation. We evaluated the site-dependent production of angiogenic growth factors in the plasma of tumor bearing animals at two different sites of implantation. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were evaluated in nude mice bearing A2780, SKOV-3, or OVCAR-3 human ovarian tumors, as well as Panc-1, AsPC-1, or BxPC-3 human pancreatic tumors grown as subcutaneous (SC) xenografts or in the intraperitoneal (IP) cavity. Plasma VEGF and bFGF levels produced by two ovarian tumor lines and two pancreatic tumor lines were substantially higher when the tumors were implanted in the IP cavity than in the SC space. These studies indicated that the site of tumor implantation was an important determinant in the production of plasma VEGF and bFGF levels. As more and more anti-angiogenic agents are developed, the need for appropriate animal models becomes apparent. These results suggest the demand for an appropriate model for the in vivo evaluation of anti-angiogenesis.
Keyes
Kristan A
KA
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. keyes@mpi.com
Mann
Larry
L
Teicher
Beverly
B
Alvarez
Enrique
E
D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2