p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma.
p75NTR, 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 p75NTR. However, the functions of these two receptors in renal cell carcinoma (RCC) have never been investigated. An overexpression of p75NTR, pro-BDNF, and to a lesser extent for TrkB and sortilin, was detected by immunohistochemistry in a cohort of 83 clear cell RCC tumors. p75NTR, 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 p75NTR as provided by p75NTR RNA silencing or blocking anti-p75NTR 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 p75NTR in renal cancer and indicate a putative novel target therapy in RCC.
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.
Miguel A
MA
De la Cruz-Morcillo
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.|Department of Urology, University Hospital Limoges, 87042 Limoges, Cedex, France.
Julien
J
Berger
PCTCLM/CRIB Unidad de Medicina Molecular Laboratorio de Oncología/Unidad de Biomedicina UCLM-CSIC, Universidad de Castilla la Mancha, 02006 Albacete, Spain.
Ricardo
R
Sánchez-Prieto
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.
Sofiane
S
Saada
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.
Thomas
T
Naves
Department of Pathology, University Hospital Limoges, 87042 Limoges, Cedex, France.
Angélique
A
Guillaudeau
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.
Aurélie
A
Perraud
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.
Philippe
P
Sindou
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.
Aurélie
A
Lacroix
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.|Department of Urology, University Hospital Limoges, 87042 Limoges, Cedex, France.
Aurélien
A
Descazeaud
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.
Fabrice
F
Lalloué
Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France.
Marie-Odile
MO
Jauberteau
D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis; D000368:Aged; D000369:Aged, 80 and over; D019138:Antibodies, Blocking / Q000494:pharmacology; D001706:Biopsy; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D005260:Female; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D020813:Receptor, trkB / Q000096:biosynthesis / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D019138:Antibodies, Blocking; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D034741:RNA, Small Interfering; D020813:Receptor, trkB; D017475:Receptors, Nerve Growth Factor; D000099183:Sortilin; C484065:NGFR protein, human; C426674:brain-derived neurotrophic factor precursor; C049985:staurosporine aglycone; C000591259:tropomyosin-related kinase-B, human
TrkB; p75NTR; pro-BDNF; renal cell carcinoma; sortilin