| First Author | Liu X | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 512 |
| Issue | 3 | Pages | 544-551 |
| PubMed ID | 30914199 | Mgi Jnum | J:291674 |
| Mgi Id | MGI:6442444 | Doi | 10.1016/j.bbrc.2019.03.136 |
| Citation | Liu X, et al. (2019) IFNgamma inhibits fibroblast-leading tumor cell invasion through downregulating N-cadherin. Biochem Biophys Res Commun 512(3):544-551 |
| abstractText | Tumor metastasis accounts for most tumor-associated mortality and is closely related with stromal fibroblasts in the tumor microenvironment. It was reported that fibroblasts promoted tumor metastasis through directly leading tumor cell invasion; however, inflammatory microenvironment in the growing tumor may influence the outcome. Here, we found that the cytokine IFNgamma, a key immune mediator secreted by T cells, could alter mouse lung tumor associated fibroblast-leading LLC tumor cell invasion in Matrigel. The motility of fibroblasts and adhesion with tumor cells were dramatically impaired upon IFNgamma stimulation. We further found that IFNgamma reduced the expression of N-cadherin on the surface of fibroblasts through upregulating SMAD7 and suppressing the downstream SMAD2 phosphorylation. N-cadherin was essential for fibroblast motility and adhesions with tumor cells. Moreover, fibroblasts could promote tumor progression and the deficiency of IFNgammaR signaling in fibroblasts reduced liver metastasis of LLC tumor in vivo. Collectively, our results demonstrate that IFNgamma inhibits fibroblast-leading tumor cell invasion by inhibiting the motility of fibroblasts and their adhesion with tumor cells. The findings indicate that inflammatory cytokines in the tumor microenvironment may regulate the fibroblast-associated tumor metastasis. |
