Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via ?-hydroxybutyrate.

ABSTRACT: Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitro and in vivo. We show that ?-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, ?-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with ?-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via ?-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.

SUBMITTER: Huang CK 

PROVIDER: S-EPMC5353665 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature