M-CSF from cancer cells induces fatty acid synthase and PPARβ/δ activation in tumor myeloid cells, leading to tumor progression

Jonghanne Park, Sang Eun Lee, Jin Hur, Eun Byeol Hong, Jae Il Choi, Ji Min Yang, Ju Young Kim, Young Chan Kim, Hyun Jai Cho, Jeffrey M. Peters, Seung Bum Ryoo, Young Tae Kim, Hyo Soo Kim

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

We investigate crosstalk between cancer cells and stromal myeloid cells. We find that Lewis lung carcinoma cells significantly induce PPARβ/δ activity in myeloid cells invitro and invivo. Myeloid cell-specific knockout of PPARβ/δ results in impaired growth of implanted tumors, and this is restored by adoptive transfer of wild-type myeloid cells. We find that IL-10 is a downstream effector of PPARβ/δ and facilitates tumor cell invasion and angiogenesis. This observation is supported by the finding that the CD11blowIL-10+ pro-tumoral myeloid cell is scarcely detected in tumors from myeloid-cell-specific PPARβ/δ knockout mice, where vessel densities are also decreased. Fatty acid synthase (FASN) is shown to be an upstream regulator of PPARβ/δ in myeloid cells and is induced by M-CSF secreted from tumor cells. Our study gives insight into how cancer cells influence myeloid stromal cells to get a pro-tumoral phenotype.

Original languageEnglish (US)
Pages (from-to)1614-1625
Number of pages12
JournalCell Reports
Volume10
Issue number9
DOIs
StatePublished - Mar 10 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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