Li Y, Chang Q, Rubin B P, Fletcher Cdm, Morgan T W, Mentzer S J, Sugarbaker D J, Fletcher J A, Xiao S
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
J Pathol. 2007 Apr;211(5):550-554. doi: 10.1002/path.2136.
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.
已知孤立性纤维瘤（SFT）会过度表达胰岛素样生长因子2（IGF-2）。然而，IGF-2的下游致癌途径尚不清楚。在此我们报告，SFT中胰岛素受体（IR）途径呈一致激活状态，SFT是一种常与低血糖相关的间充质肿瘤。虽然IR及其下游信号通路在SFT中持续激活，但胰岛素样生长因子1受体（IGF-1R）在这些肿瘤中未表达。我们还发现，SFT细胞分泌IGF-2并在无血清培养基中增殖，这与IGF-2/IR自分泌环一致所有SFT中均有对IGF-2具有高亲和力的IR亚型IR-A的表达，这支持了IGF-2在病因学上的相关性。我们的研究表明，IR激活在SFT中发挥致癌作用。
