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
Affiliations
Jonghanne Park
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Sang Eun Lee
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Jin Hur
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Eun Byeol Hong
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Jae-Il Choi
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Ji-Min Yang
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Ju-Young Kim
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Young-Chan Kim
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Hyun-Jai Cho
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
Jeffrey M. Peters
Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, PA 16802, USA
Seung-Bum Ryoo
Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea
Young Tae Kim
Department of Thoracic and Cardiovascular Surgery, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea
Hyo-Soo Kim
National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea
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.
