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.