title: M-CSF from Cancer Cells Induces Fatty Acid Synthase and PPARβ/δ Activation in Tumor Myeloid Cells, Leading to Tumor Progression.
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 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.
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea; Cardiovascular Center and Department of Internal Medicine, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Jonghanne
authors.initials: J
authors.lastname: Park
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea; Cardiovascular Center and Department of Internal Medicine, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Hur
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Eun Byeol
authors.initials: EB
authors.lastname: Hong
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Yang
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Young-Chan
authors.initials: YC
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea; Cardiovascular Center and Department of Internal Medicine, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Hyun-Jai
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Peters
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: Seung-Bum
authors.initials: SB
authors.lastname: Ryoo
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell Niche, Seoul National University Hospital, Seoul 110-744, Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul 110-744, Korea; Cardiovascular Center and Department of Internal Medicine, Seoul National University Hospital, Seoul 110-744, Korea; Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science Technology, Seoul National University, Seoul 110-799, Korea. Electronic address: hyosoo@snu.ac.kr.
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim