Insulin-like growth factor family in malignant haemangiopericytomas: the expression and role of insulin-like growth factor I receptor.
Haemangiopericytoma is a rare soft tissue tumour originating from the contractile pericapillary cells. Relatively little is known about its molecular pathogenesis. To address this issue, the insulin-like growth factor family (IGFs) was analysed in 19 tumours collected from a human tumour bank network. Seven of the tumours were associated with severe hypoglycaemia. Of these, six were retroperitoneal and one was located in the leg. 3 out of the 19 tumours (15.8 per cent) were positive for insulin-like growth factor I (IGF I) mRNA and 11 were positive for IGF II mRNA (57.9 per cent). Almost 90 per cent of haemangiopericytomas expressed IGF I receptor (IGF IR) mRNA (17 out of 19), five (26.3 per cent) expressed IGF binding protein 1 (IGF BP1), three (15.8 per cent) expressed IGF BP2, and four (21 per cent) exhibited IGF BP3 mRNA. All of the 14 haemangiopericytomas examined with regard to specific receptor binding were IGF IR positive, ranging from 1.2 to 16.2 per cent. Binding was much higher in IGF I/IGF IR positive tumours (15.3+/-0. 7) than in IGF I negative/IGF IR positive tumours (5.1+/-3.3). The potential role of IGF IR as a growth promoting factor in malignant haemangiopericytoma was studied using antisense oligonucleotides and monoclonal antibody alphaIR3 that specifically inhibit IGF IR synthesis or activity. 10 microM IGF IR antisense oligonucleotides significantly inhibited the growth of haemangiopericytoma cells in culture, by around 50 per cent; monoclonal antibody against IGF IR (alphaIR3) also significantly inhibited proliferation. The data suggest that IGF IR may play an important role in the genesis and progression of malignant haemangiopericytomas.
Pavelić
K
K
Division of Molecular Medicine, Ruder Bosković Institute, HR-10000 Zagreb, Croatia. pavelic@rudjer.irb.hr
Pavelić
Z P
ZP
Cabrijan
T
T
Karner
I
I
Samarzija
M
M
Stambrook
P J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D002455:Cell Division; D002675:Child, Preschool; D005260:Female; D006393:Hemangiopericytoma / Q000097:blood / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010386:Pelvic Neoplasms / Q000737:chemistry / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D012186:Retroperitoneal Neoplasms / Q000097:blood / Q000737:chemistry* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013002:Somatomedins / Q000032:analysis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1