Responsiveness of stromal fibroblasts to IFN-gamma blocks tumor growth via angiostasis.
The importance of stromal cells for tumor is akin to soil for seed. However, the interaction among these cells is far from understood. In this study, we show that stromal fibroblasts exist not only during tumor progression but also during regression stage, together with immune effector cells. Coinjection of stromal fibroblasts with tumor cells often promotes tumor growth. However, the presence of IFN-gamma significantly impairs the ability of these cells to promote tumor growth due to a reduced angiogenesis. The mechanism relies mainly on the IFN-gamma-mediated down-regulation of vascular endothelial growth factor production by fibroblasts. The results reveal a novel link between immune cells and nonbone marrow-derived stromal cells, and define stromal fibroblasts as the main targets of IFN-gamma in tumor immunity.
Lu
Yu
Y
National Laboratory of Biomacromolecules, Graduate School of the Chinese Academy of Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Yang
Wei
W
Qin
Chuan
C
Zhang
Lianfeng
L
Deng
Jingjing
J
Liu
Shubai
S
Qin
Zhihai
Z
D000818:Animals; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology* / Q000378:metabolism; D000096743:Interferon gamma Receptor
D054377:Chemokine CXCL12; D007371:Interferon-gamma; D020778:Matrix Metalloproteinase 2; D017471:Receptors, Interferon; D042461:Vascular Endothelial Growth Factor A; D000096743:Interferon gamma Receptor; C515256:Cxcl12 protein, mouse; C522362:Mmp2 protein, mouse