Serum insulin-like growth factors (IGFs) and IGF binding protein (IGFBP)-3 in patients with gastric cancer: IGFBP-3 protease activity induced by surgery

Recent findings have indicated that insulin-like growth factors (IGF-I and IGF-II) may play a role in neoplasia. Alteration of serum IGFs or IGF Binding Proteins (IGFBPs) have been reported in some tumors. In this study, we measured serum IGF-I, IGF-II and IGFBPs profile in gastric cancer by radioimmunoassay and Western ligand blots. The serum IGF-I level in gastric cancer was significantly lower than in control subjects (65.2±26.5 vs 148.4±55.2 ng/ml, p<0.01) and was further decreased to 45.5±20.9 ng/ml after surgery. The serum IGF-II level was slightly higher than that in control subjects (826.3±360.2 vs 735.7±154.6 ng/ml) but it was significantly decreased after surgery (525.7± 220.1 ng/ml, p<0.05). The serum IGFBP-3 level was not significantly different from those in control subjects. However, we observed a decreased level of serum IGFBP-3 after surgery, and incubation of postoperative serum with control serum resulted in a significant reduction of IGFBP-3 level. The reduction of IGFBP-3 in postoperative serum was mainly due to surgery associated IGFBP-3 protease activity. This protease activity was totally inhibited by aprotinin, EDTA and PMSF but not by pepstatin and leupeptin. This inhibition pattern is consistant with cation dependent serine protease. We speculate that proteolysis of IGFBP-3 may contribute to increase the bioavailability of IGFs.