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.

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.