M-CSF from Cancer Cells Induces Fatty Acid Synthase and PPARβ/δ Activation in Tumor Myeloid Cells, Leading to Tumor Progression
2015
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
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 in vitro and in vivo. 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.
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