TY  - JOUR
ID  - 20603072
AU  - Cruz-Munoz, William
AU  - Jaramillo, Maria L.
AU  - Man, Shan
AU  - Xu, Ping
AU  - Banville, Myriam
AU  - Collins, Catherine
AU  - Nantel, Andre
AU  - Morgan, Sherif S.
AU  - Cranmer, Lee D.
AU  - O'Connor-McCourt, Maureen D.
AU  - Kerbel, Robert S.
T1  - Roles for endothelin receptor B and BCL2A1 in spontaneous CNS metastasis of melanoma
JO  - Cancer Research
SP  - 1
EP  - 29
PY  - 2012
N2  - Metastatic 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.
M1  - 53130
DO  - http://dx.doi.org/10.1158/0008-5472.CAN-12-2194
U3  - NRC Biotechnology Research Institute
U3  - Institut de recherche en biotechnologie du CNRC
U3  - National Research Council Canada
U3  - Conseil national de recherches Canada
ER  -