title: Differential roles of Trk and p75 neurotrophin receptors in tumorigenesis and chemoresistance ex vivo and in vivo.
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.
authors.affiliation: Lady Davis Research Institute, Jewish General Hospital, McGill University, 3755 Cote Ste-Catherine E-535, Montreal, QC, H3T 1E2, Canada.
authors.forename: Muriel
authors.initials: M
authors.lastname: Bassili
authors.forename: Elena
authors.initials: E
authors.lastname: Birman
authors.forename: Nina F
authors.initials: NF
authors.lastname: Schor
authors.forename: H Uri
authors.initials: HU
authors.lastname: Saragovi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D016716:PC12 Cells; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D020917:Receptor, trkA / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D020800:Receptor, Nerve Growth Factor; D004317:Doxorubicin; D020917:Receptor, trkA; D002945:Cisplatin
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