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

Abstract

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 analyzed insulin-like growth factor (IGF) II and IGF I receptor in 29 tumors collected from a human tumor bank network. Seven of these tumors were associated with severe hypoglycemia; six were retroperitoneal and one was located in the leg. Of 22 tumors tested 12 (54.5%) exhibited IGF II mRNA, while almost 90% (17 of 19) of hemangiopericytomas exhibited IGF I receptor mRNA. Sera from some patients whose tumors expressed IGF II mRNA contained elevated levels of IGF II. Removal of the tumor eliminated most of the IGF II immunoreactivity from the sera. The potential role of IGF II as a growth-promoting factor was examined on three malignant primary hemangiopericytoma cell cultures. Extracellular addition of IGF II significantly enhanced cell proliferation in a dose-dependent manner. Antisense oligodeoxynucleotides that specifically inhibit IGF II mRNA, at a concentration of 40 or 80 micrograms/ml, inhibited the growth of hemangiopericytoma cells significantly, by 40%. Simultaneous administration of antisense deoxyoligonucleotides to both IGF II and IGF I receptor inhibited tumor cell proliferation by even 80%. Our data suggest that tumor cells produce IGF II, and that this in turn stimulates their proliferation by autocrine mechanisms.

The Role of Insulin-Like Growth Factor 1 in the Development of Benign and Malignant Thyroid Nodules

“…Cell culture experiments and clinical studies revealed that GH and IGF-1 axis may have a role in neoblastic activity, and overproduction of IGFs act as stimulators of malignant cell proliferation (7,20,24,25). A previous study showed IGF-1 positivity in 38 out of 53 patients with thyroidal cancer, and current data confirmed the link between the papillary cancer and elevated tissue levels of IGF-1 (20).…”

Insulin-like growth factor 2 and its receptors (IGF 1R and IGF 2R/mannose 6-phosphate) in endometrial adenocarcinoma

“…Together with the fact that almost all such samples had a decreased apoptosis rate, the increased proliferation index, as well as increased telomerase activity, indicate the important role of proteins of the IGF family in the pathogenesis of endometrial adenocarcinoma. Similar finding were also shown for colon [3], lung [8], gastric [10] and gynecological cancers [19], as well as hemangiopericytomas [20]. Furthermore, all these data [26] showed that in HEC-1A endometrial adenocarcinoma cells responsive to IGF 1, the IGF BP3 is the main binding protein expressed, and both soluble and cell-associated forms act as inhibitors of IGF 1-induced cellular proliferation.…”

IGF2 and cancer

“…In HCC, however, it performed poorly as a tumour marker compared with methylation analysis and alphafetoprotein (Morace et al 2010). IGF2 concentrations decrease following surgery, which suggests utility in monitoring tumour burden (Pavelic et al 1999, Fukuda et al 2006. However, its use could be limited in tumours, which do not secrete IGF2 throughout the disease course.…”