Oncogenic functions of IGF1R and INSR in prostate cancer include enhanced tumor growth, cell migration and angiogenesis
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Isabel Heidegger1, Johann Kern2, Philipp Ofer1, Helmut Klocker1,* and Petra Massoner1,*
1 Division of Experimental Urology, Department of Urology, Innsbruck Medical University, Innsbruck, Austria
2 Department of Hematology and Oncology, Innsbruck Medical University, Innsbruck, Austria
* The last two authors made equal contributions to the study
Helmut Klocker, email:
Petra Massoner, email:
Keywords: Prostate cancer, IGF targeting therapies, insulin-like growth factor receptor-1 (IGF1R), insulin receptor (INSR).
Received: February 14, 2014 Accepted: April 01, 2014 Published: April 02, 2014
We scrutinized the effect of insulin receptor (INSR) in addition to IGF1R in PCa using in vitro and in vivo models. In-vitro overexpression of IGF1R and INSRA, but not INSRB increased cell proliferation, colony formation, migration, invasion and resistance to apoptosis in prostate cancer cells (DU145, LNCaP, PC3). Opposite effects were induced by downregulation of IGF1R and total INSR, but not INSRB. In contrast to tumor cells, non-cancerous epithelial cells of the prostate (EP156T, RWPE-1) were inhibited on overexpression and stimulated by knockdown of receptors. In-vivo analyses using the chicken allantoic membrane assay confirmed the tumorigenic effects of IGF1R and INSR. Apart from promoting tumor growth, IGF1R and INSR overexpression also enhanced angiogenesis indicated by higher vessel density and increased number of desmin-immunoreactive pericytes. Our study underscores the oncogenic impact of IGF1R including significant effects on tumor growth, cell migration, sensitivity to apoptotic/chemotherapeutic agents and angiogenesis, and characterizes the INSR, in particular the isoform INSRA, as additional cancer-promoting receptor in prostate cancer. Both, the insulin-like growth factor receptor 1 and the insulin receptor exert oncogenic functions, thus proposing that both receptors need to be considered in therapeutic settings.
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