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Nature. 2017 Jan 5;541(7635):41-45. doi: 10.1038/nature20791. Epub 2016 Dec 7.

Targeting metastasis-initiating cells through the fatty acid receptor CD36.

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.
2
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, 08003 Barcelona, Spain.
3
IMIM, Department of Dermatology, Hospital del Mar, 08003 Barcelona.
4
Vall D´Hebron Hospital, Barcelona, Department of Oral and Maxillofacial Surgery, Universitat Autònoma de Barcelona, Barcelona 08035 Spain.
5
Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain.
6
Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain.

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.

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PMID:
27974793
DOI:
10.1038/nature20791
[Indexed for MEDLINE]

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