Targeting metastasis-initiating cells through the fatty acid receptor CD36
Author: ["Gloria Pascual","Alexandra Avgustinova","Stefania Mejetta","Mercè Martín","Andrés Castellanos","Camille Stephan-Otto Attolini","Antoni Berenguer","Neus Prats","Agustí Toll","Juan Antonio Hueto","Coro Bescós","Luciano Di Croce","Salvador Aznar Benitah"]
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Abstract
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 CD44bright 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. Human oral carcinoma cells expressing high levels of the fatty acid receptor CD36 initiate metastasis in mouse models, and metastasis is increased by palmitic acid or a fatty diet and decreased by blockade of CD36. The ability to identify cells with metastatic potential is of clinical importance for the development of anti-metastatic treatment. Salvador Aznar Benitah and colleagues have identified high metastatic potential in a population of cells expressing high levels of the fatty acid receptor CD36 in human oral carcinoma samples. The cells initiate metastasis in mouse models. Metastasis is increased by palmitic acid or a fatty diet, and decreased by CD36 blockade.
Cite this article
Pascual, G., Avgustinova, A., Mejetta, S. et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 541, 41–45 (2017). https://doi.org/10.1038/nature20791
