TY - JOUR
T1 - Targeting metastasis-initiating cells through the fatty acid receptor CD36
AU - Pascual, Gloria
AU - Avgustinova, Alexandra
AU - Mejetta, Stefania
AU - Martín, Mercè
AU - Castellanos, Andrés
AU - Attolini, Camille Stephan Otto
AU - Berenguer, Antoni
AU - Prats, Neus
AU - Toll, Agustí
AU - Hueto, Juan Antonio
AU - Bescós, Coro
AU - Di Croce, Luciano
AU - Benitah, Salvador Aznar
PY - 2017/1/5
Y1 - 2017/1/5
N2 - The fact that the identity of the cells that initiate metastasis in most human cancers is unknown hampers the development of antimetastatic therapies. Here we describe a subpopulation of CD44 bright cells in human oral carcinomas that do not overexpress mesenchymal genes, are slow-cycling, express high levels of the fatty acid receptor CD36 and lipid metabolism genes, and are unique in their ability to initiate metastasis. Palmitic acid or a high-fat diet specifically boosts the metastatic potential of CD36 + metastasis-initiating cells in a CD36-dependent manner. The use of neutralizing antibodies to block CD36 causes almost complete inhibition of metastasis in immunodeficient or immunocompetent orthotopic mouse models of human oral cancer, with no side effects. Clinically, the presence of CD36 + metastasis-initiating cells correlates with a poor prognosis for numerous types of carcinomas, and inhibition of CD36 also impairs metastasis, at least in human melanoma- and breast cancer-derived tumours. Together, our results indicate that metastasis-initiating cells particularly rely on dietary lipids to promote metastasis.
AB - The fact that the identity of the cells that initiate metastasis in most human cancers is unknown hampers the development of antimetastatic therapies. Here we describe a subpopulation of CD44 bright cells in human oral carcinomas that do not overexpress mesenchymal genes, are slow-cycling, express high levels of the fatty acid receptor CD36 and lipid metabolism genes, and are unique in their ability to initiate metastasis. Palmitic acid or a high-fat diet specifically boosts the metastatic potential of CD36 + metastasis-initiating cells in a CD36-dependent manner. The use of neutralizing antibodies to block CD36 causes almost complete inhibition of metastasis in immunodeficient or immunocompetent orthotopic mouse models of human oral cancer, with no side effects. Clinically, the presence of CD36 + metastasis-initiating cells correlates with a poor prognosis for numerous types of carcinomas, and inhibition of CD36 also impairs metastasis, at least in human melanoma- and breast cancer-derived tumours. Together, our results indicate that metastasis-initiating cells particularly rely on dietary lipids to promote metastasis.
U2 - https://doi.org/10.1038/nature20791
DO - https://doi.org/10.1038/nature20791
M3 - Article
VL - 541
SP - 41
EP - 45
ER -
