Cancer Chemotherapy and Pharmacology

, Volume 65, Issue 6, pp 1047–1056

Differential roles of Trk and p75 neurotrophin receptors in tumorigenesis and chemoresistance ex vivo and in vivo

  • Muriel Bassili
  • Elena Birman
  • Nina F. Schor
  • H. Uri Saragovi
Original Article

Abstract

The neurotrophin receptors TrkA (NGF receptor) and TrkC (NT-3 receptor) have been shown to be important in staging disease and predicting progression and drug response for various neoplasias such as neuroblastoma, medulloblastoma and prostate cancer. Less is known about the role of the p75 neurotrophin receptor in cancer, but it influences metastatic potential in glioblastoma. To determine the effect of each neurotrophin receptor or co-receptor expression in tumorigenesis, we examined PC12 pheochromocytomas. PC12 wild type (TrkA+, p75++) were compared to three PC12-derived cell lines expressing varying levels of TrkA or TrkC and/or p75. Growth rates, tumorigenic potential ex vivo and in vivo, and chemotherapeutic drug response profiles differed depending on the neurotrophin receptor phenotype. The ability of neurotrophins to rescue cells from doxorubicin or cisplatin induced cell death also varied depending on phenotype. Thus, unique neurotrophin receptor tumor profiles may determine tumor aggressiveness and chemoresistance. This work may help to develop tailored therapies for specific tumor phenotypes by combining traditional chemotherapy with neurotrophin receptor modulators.

Keywords

Neurotrophin Receptor Trk p75 Neural crest tumors Growth kinetics Tumorigenic potential Drug resistance 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Muriel Bassili
    • 1
  • Elena Birman
    • 1
  • Nina F. Schor
    • 4
  • H. Uri Saragovi
    • 1
    • 2
    • 3
  1. 1.Lady Davis Research Institute, Jewish General HospitalMcGill UniversityMontrealCanada
  2. 2.Department of Pharmacology and TherapeuticsMcGill UniversityMontrealCanada
  3. 3.Department of Oncology and the Cancer CentreMcGill UniversityMontrealCanada
  4. 4.Department of PediatricsGolisano Children’s Hospital at URMC, University of Rochester Medical CenterRochesterUSA

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