EVALUATION OF THE BALANCE BETWEEN ANGIOGENIC AND ANTIANGIOGENIC CIRCULATING FACTORS IN PATIENTS WITH BREAST AND GASTROINTESTINAL CANCERS

Angiogenesis is a critical determinant of tumor growth. Tumor cells pr oduce or induce angiogenic molecules that act specifically on endothel ial cells (ECs) but also release angiostatic molecules. Thus, tumor an giogenesis represents a net balance between positive and negative regu lators of neovascularization, Sera from patients with breast or gastro intestinal cancers were evaluated for their capacity to selectively mo dulate the proliferation of human umbilical vein ECs; sera from 15 of 78 (19%) breast cancer patients and 8 of 53 (15%) gastrointestinal can cer patients induced human umbilical vein EC growth, whereas sera from 4 of 78 (5%) breast cancer patients and 1 of 53 (2%) gastrointestinal cancer patients inhibited EC proliferation. Growth-stimulatory sera w ere significantly more frequent among postmenopausal (14 of 53) than p remenopausal (1 of 25) breast cancer patients; inhibitory activity was observed in 3 of 25 premenopausal patients versus 1 of 53 postmenopau sal individuals. The half-life of serum-stimulating and -inhibiting fa ctors seemed to differ, because stimulatory activity but not inhibitor y activity was decreased at 5 days after surgery. The levels of vascul ar endothelial growth factor were elevated in about 45% of patients wi th growth-stimulatory sera, whereas the serum inhibition of EC growth was found to be due, at least in part, to high levels of soluble throm bospondin.