Activation of mesenchymal stem cells by macrophages prompts human gastric cancer growth through NF-κB pathway.
Accumulating evidence indicate that macrophages activate mesenchymal stem cells (MSCs) to acquire pro-inflammatory phenotype. However, the role of MSCs activated by macrophages in gastric cancer remains largely unknown. In this study, we found that MSCs were activated by macrophages to produce increased levels of inflammatory cytokines. Cell colony formation and transwell migration assays revealed that supernatants from the activated MSCs could promote both gastric epithelial cell and gastric cancer cell proliferation and migration. In addition, the expression of epithelial-mesenchymal transition (EMT), angiogenesis, and stemness-related genes was increased in activated MSCs. The phosphorylated forms of NF-κB, ERK and STAT3 in gastric cells were increased by active MSCs. Inhibition of NF-κB activation by PDTC blocked the effect of activated MSCs on gastric cancer cells. Co-injection of activated MSCs with gastric cancer cells could accelerate gastric cancer growth. Moreover, human peripheral blood monocytes derived macrophages also activated MSCs to prompt gastric cancer cell proliferation and migration. Taken together, our findings suggest that MSCs activated by macrophage acquire pro-inflammatory phenotype and prompt gastric cancer growth in an NF-κB-dependent manner, which provides new evidence for the modulation of MSCs by tumor microenvironment and further insight to the role of stromal cells in gastric carcinogenesis and cancer progression.
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Tingting
T
Yang
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Xu
X
Zhang
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Mei
M
Wang
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Jie
J
Zhang
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Feng
F
Huang
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Jie
J
Cai
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Qiang
Q
Zhang
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Fei
F
Mao
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Wei
W
Zhu
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Hui
H
Qian
School of Medical Science and Laboratory Medicine, Jiangsu University Zhenjiang, Jiangsu, China; The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Wenrong
W
Xu
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D014410:Tumor Stem Cell Assay
D016207:Cytokines; D016328:NF-kappa B