Roles for endothelin receptor B and BCL2A1 in spontaneous CNS metastasis of melanoma

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DOIResolve DOI: http://doi.org/10.1158/0008-5472.CAN-12-2194
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TypeArticle
Journal titleCancer Research
Pages129; # of pages: 29
AbstractMetastatic spread of melanoma to CNS is a common and devastating manifestation of disease progression, which, despite its clinical importance, remains poorly understood with respect to undelying molecular mechanisms. Using a recently developed preclinical model of spontaneous melanoma CNS metastasis, we have identified alterations in expression of endothelin receptor B (ednrb) as a potential factor that influences brain metastatic potential. Induced overexpression of this gene mediated enhanced overall metastatic disease, and resulted in an increased incidence of spontaneous CNS metastases. In contrast, the overexpression of other highlighted genes, such as bcl2a1, did not affect the incidence of CNS metastases but nevertheless appears to facilitate intracranial tumor growth. The pro-metastatic effect in the CNS associated with EDNRB appears to be mediated by the interaction with its ligands resulting in enhanced tumor cell proliferation and thus intracranial melanoma growth. That EDRNB contributes to melanoma metastasis is underscored by the fact that its therapeutic inhibition by the EDNRB-specific inhibitor, A192621, translated into improved outcomes when treating mice with either visceral metastases or intracranial tumors. The identification of an influential role of EDNRB in CNS melanoma spontaneous metastasis may provide both a target for therapeutic intervention as well as a potential prognostic marker for patients having an increased predisposition for incidence of CNS melanoma metastases.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedYes
NRC number53130
NPARC number20603072
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Record identifiercfbc86eb-508d-4937-9fe1-26f3f9548fdd
Record created2012-09-13
Record modified2016-05-09
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