title: Bone marrow-derived myofibroblasts promote colon tumorigenesis through the IL-6/JAK2/STAT3 pathway.
abstract: Bone marrow-derived myofibroblasts (BMFs) have been shown to promote tumor growth. Here, we found that BMFs or BMF conditioned medium (BMF-CM) induced cancer stem cell-like sphere formation of colon cancer cells. The co-cultured BMFs, but not co-cultured cancer cells, expressed higher levels of IL-6 than BMFs or cancer cells cultured alone. Anti-mouse IL-6 neutralizing antibody, JAK2 inhibitors and STAT3 knockdown in mouse cancer cells reduced BMF- and BMF-CM-induced sphere formation of colon cancer cells. When co-injected, BMFs significantly enhanced tumorigenesis of colon cancer cells in mice. Our results demonstrate that BMFs promote tumorigenesis via the activation of the IL-6/JAK2/STAT3 pathway.
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Liming
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Jindong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Yunlin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Emergency Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Emergency Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Medicine, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: tushuiping@yahoo.com.
authors.forename: Shui Ping
authors.initials: SP
authors.lastname: Tu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000473:pathology*; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058628:Myofibroblasts / Q000166:cytology*; D009368:Neoplasm Transplantation; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
keywords: BMF conditioned medium; BMF-CM; BMFs; Bone marrow-derived myofibroblasts; CAFs; Cancer stem cell; Co-culture-CM; Colon cancer; EGF; FL; IL-6; JAK2; MSCs; STAT3; TGF-β; bFGF; basic fibroblast growth factor; bone marrow-derived myofibroblasts; cancer-associated fibroblasts; co-culture medium of BMFs and cancer cells; epithelial growth factor; firefly luciferase; interleukin-6; janus kinase 2; mesenchymal stem cells; signal transducer and activator of transcription 3; transformation growth factor-β