engleski

The expression and role of insulin-like growth factor II in malignant hemangiopericytomas

Hemangiopericytoma is a rare soft tissue tumor originating from contractile pericapillary pericytes. To address the issue of molecular genetic events that participate in genesis and progression of hemangiopericytoma, we analysed insulin-like growth factor II and insulin-like growth factor I receptor in 29 tumors collected from a human tumor bank network. Among them, seven tumors were associated with severe hypoglycemia. Of these, six tumors were retroperitoneal and one was located in the leg. Twelve out of twenty two (54.5%) tumors tested exhibited insulin-like growth factor II mRNA whereas almost 90% (17 out of 19) of hemangiopericytomas exhibited insulin-like growth factor I receptor mRNA. Sera from some patients whose tumors expressed insulin-like growth factor II mRNA contained elevated level of insulin-like growth factor II. Removal of the tumor eliminated most of the insulin-like growth factor II immunoreactivity from the sera. The potential role of insulin-like growth factor II as a growth promoting factor was examined on three malignant primary hemangiopericytoma cell cultures. Extracellular addition of insulin-like growth factor II significantly enhanced cell proliferation in a dose-dependent manner. Antisense oligodeoxynucleotides that specifically inhibit insulin-like growth factor II mRNA, in concentration of 40 or 80 mg/ml, inhibited the growth of hemangiopericytoma cells significantly - by 40%. Simultaneous application of antisense deoxyoligonucleotides to both insulin-like growth factor II and insulin-like growth factor I receptor inhibited tumor cell proliferation by even 80%. Our data suggest that tumor cells produce insulin-like growth factor II which in turn stimulate their proliferation by autocrine mechanisms.

hemangiopericytoma; insulin-like growth factor II; insulin-like growth factor I receptor

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