Targeting Metastasis-initiating Cells Through the Fatty Acid Receptor CD36

Overview

Journal Nature

Specialty Science

Date 2016 Dec 16

PMID 27974793

Citations 685

Authors

Gloria Pascual

Alexandra Avgustinova

Stefania Mejetta

Merce Martin

Andres Castellanos

Camille Stephan-Otto Attolini

Antoni Berenguer

Neus Prats

Agusti Toll

Juan Antonio Hueto

Coro Bescos

Luciano Di Croce

Salvador Aznar Benitah

Affiliations

Soon will be listed here.

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 CD44 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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