p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma

p75(NTR), a member of TNF receptor family, is the low affinity receptor common to several mature neurotrophins and the high affinity receptor for pro-neurotrophins. Brain-Derived Neurotrophic Factor (BDNF), a member of neurotrophin family has been described to play an important role in development and progression of several cancers, through its binding to a high affinity tyrosine kinase receptor B (TrkB) and/or p75(NTR). However, the functions of these two receptors in renal cell carcinoma (RCC) have never been investigated. An overexpression of p75(NTR), pro-BDNF, and to a lesser extent for TrkB and sortilin, was detected by immunohistochemistry in a cohort of 83 clear cell RCC tumors. p75(NTR), mainly expressed in tumor tissues, was significantly associated with higher Fuhrman grade in multivariate analysis. In two derived-RCC lines, 786-O and ACHN cells, we demonstrated that pro-BDNF induced cell survival and migration, through p75(NTR) as provided by p75(NTR) RNA silencing or blocking anti-p75(NTR) antibody. This mechanism is independent of TrkB activation as demonstrated by k252a, a tyrosine kinase inhibitor for Trk neurotrophin receptors. Taken together, these data highlight for the first time an important role for p75(NTR) in renal cancer and indicate a putative novel target therapy in RCC.