Shift in the Balance between Circulating Thrombospondin-1 and Vascular Endothelial Growth Factor in Cancer Patients: Relationship to Platelet α-Granule Content and Primary Activation

Abstract

Tumoral angiogenesis is regulated by the balance between factors that activate and inhibit angiogenesis. Elevated levels of activators have been associated with a poor prognosis in cancer patients, but little is known about the net balance between circulating activators and inhibitors in these patients. This study was designed to determine whether the balance between circulating concentrations of the angiogenesis inhibitor TSP-1 and the activator VEGF differs from that in healthy persons, and to shed light on the possible role of platelets in this balance. Twenty-five cancer patients and 18 healthy subjects were included. Serum and plasma concentrations of VEGF, TSP-1 and PF4 were measured by ELISA. Our results showed that in healthy subjects the balance between the TSP-1 and VEGF concentrations in serum and in serum minus plasma was twice to three times as high as in cancer patients (p<0.05). The theoretical TSP-1 content per platelet was greater in healthy subjects than in patients (94 vs. 53.6 ng/mL, p<0.05), and platelet activation (determined indirectly as the plasma concentration of PF4) was greater in cancer patients (129 vs. 48 IU/mL, p<0.01). Platelet activation correlated significantly with serum concentration of TSP-1 (r=0.470, p=0.018) and showed a tendency toward correlation with plasma concentration of TSP-1 (r=0.382, p=0.059). Our findings show that the circulating TSP-1/VEGF balance is diminished in cancer patients. Platelet activation may play an important role in this decrease and may ultimately lead to increased angiogenic activity in these patients.