Insulin receptor activation in solitary fibrous tumours.
Solitary fibrous tumours (SFTs) are known to overexpress insulin-like growth factor 2 (IGF-2). The down-stream oncogenic pathways of IGF-2, however, are not clear. Here we report uniform activation of the insulin receptor (IR) pathway in SFTs, which are mesenchymal tumours frequently associated with hypoglycaemia. Whereas the IR and its downstream signalling pathways were constitutively activated in SFTs, insulin-like growth factor 1 receptor (IGF-1R) was not expressed in these tumours. We also find that SFT cells secrete IGF-2 and proliferate in serum-free medium, consistent with an IGF-2/IR autocrine loop. The aetiological relevance of IGF-2 is supported by expression of IR-A, the IR isoform with high affinity for IGF-2, in all SFTs. Our studies suggest that IR activation plays an oncogenic role in SFTs.
Li
Y
Y
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Chang
Q
Q
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Rubin
B P
BP
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Fletcher
Cdm
C
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Morgan
T W
TW
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Mentzer
S J
SJ
Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Sugarbaker
D J
DJ
Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Fletcher
J A
JA
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Xiao
S
S
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
D000328:Adult; D000368:Aged; D016895:Culture Media, Serum-Free; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D018218:Neoplasms, Fibrous Tissue / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010997:Pleural Neoplasms / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic
D016895:Culture Media, Serum-Free; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D020928:Mitogen-Activated Protein Kinases