title: 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.
authors.affiliation: Division of Molecular Medicine, Ruder Bosković Institute, Zagreb, Croatia. pavelic@rudjer.irb.hr
authors.forename: K
authors.initials: K
authors.lastname: Pavelić
authors.forename: S
authors.initials: S
authors.lastname: Spaventi
authors.forename: V
authors.initials: V
authors.lastname: Gluncić
authors.forename: A
authors.initials: A
authors.lastname: Matejcić
authors.forename: D
authors.initials: D
authors.lastname: Pavicić
authors.forename: N
authors.initials: N
authors.lastname: Karapandza
authors.forename: Z
authors.initials: Z
authors.lastname: Kusić
authors.forename: J
authors.initials: J
authors.lastname: Lukac
authors.forename: C
authors.initials: C
authors.lastname: Dohoczky
authors.forename: T
authors.initials: T
authors.lastname: Cabrijan
authors.forename: J
authors.initials: J
authors.lastname: Pavelić
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D005260:Female; D006393:Hemangiopericytoma / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D020320:Oligoribonucleotides, Antisense; D011863:Radioimmunoassay; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D020320:Oligoribonucleotides, Antisense; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1