Targeting metastasis-initiating cells through the fatty acid receptor CD36

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 and Salvador Aznar Benitah ()
Additional contact information
Gloria Pascual: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST)
Alexandra Avgustinova: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST)
Stefania Mejetta: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST)
Mercè Martín: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST)
Andrés Castellanos: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST)
Camille Stephan-Otto Attolini: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST)
Antoni Berenguer: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST)
Neus Prats: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST)
Agustí Toll: IMIM, Hospital del Mar
Juan Antonio Hueto: Vall D´Hebron Hospital, Barcelona, Universitat Autònoma de Barcelona
Coro Bescós: Vall D´Hebron Hospital, Barcelona, Universitat Autònoma de Barcelona
Luciano Di Croce: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST)
Salvador Aznar Benitah: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST)

Nature, 2017, vol. 541, issue 7635, 41-45

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature20791

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