Circulating angiogenic growth factor levels in mice bearing human tumors using Luminex Multiplex technology.
Tumor angiogenesis is essential for tumor growth and metastasis formation. Luminex methodology was used to measure the levels of four angiogenic cytokines in cell culture medium and in the plasma of mice bearing human tumors. We obtained plasma and conditioned culture medium from 12 different human tumor cell lines. Tumor necrosis factor-alpha (TNF-alpha), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta) were determined by the Luminex FlowMetrix assay. VEGF, TNF-alpha, and bFGF were undetectable in non-tumor-bearing animals. HS746T gastric cancer and Caki-1 renal cell cancer cells in culture produced high levels of VEGF (1000 and 450 pg/10(6) cells, respectively). High levels of TGF-beta were produced by HS746T gastric carcinoma and Calu-6 non-small-cell lung carcinoma (3000 and 1000 pg/10(6) cells, respectively). Caki-1 renal cell carcinoma and Calu-6 non-small-cell lung carcinoma cells in culture produced high levels of bFGF (42 and 10 pg/10(6) cells, respectively). Caki-1, SW2 SCLC, HCT-116 and HT-29 colon tumors produced high plasma levels of VEGF (200, 220, 42, and 151 pg/ml, respectively) and TGF-beta (31, 36, 45, 32 pg/ml, respectively). A positive linear correlation was seen between tumor volume and VEGF in SW2 (r=0.87) and Caki-1 (r=0.47) tumors, and a moderate correlation in HCT116 tumors (r=0.3). Angiogenic profiles in the plasma of nude mice bearing human tumors may be useful to identify appropriate biomarkers for antiangiogenic therapy, as diagnostic and prognostic tools, and to monitor the responses of individual tumors to antiangiogenic therapy.
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Kristan A
KA
Keyes
Larry
L
Mann
Karen
K
Cox
Patti
P
Treadway
Philip
P
Iversen
Yun-Fei
YF
Chen
Beverly A
BA
Teicher
D043925:Angiogenesis Inducing Agents / Q000032:analysis / Q000097:blood*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D016228:Endothelial Growth Factors / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D007118:Immunoassay / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008222:Lymphokines / Q000097:blood; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology*; D009389:Neovascularization, Pathologic; D016212:Transforming Growth Factor beta / Q000097:blood; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2