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.
Park, J., Lee, S. E., Hur, J., Hong, E. B., Choi, J. I., Yang, J. M., … Kim, H. S. (2015). M-CSF from cancer cells induces fatty acid synthase and PPARβ/δ activation in tumor myeloid cells, leading to tumor progression. Cell Reports, 10(9), 1614–1625. https://doi.org/10.1016/j.celrep.2015.02.024