Stromal cell-derived factor 1 secreted by cancer-associated fibroblasts promotes lncRNA Xist through CXCR4 and facilitates invasion and metastasis of non-small cell lung cancer

Abstract

Cancer-associated fibroblasts (CAFs) abundantly exist in NSCLCs and promote tumor progression in most solid tumors. This study investigated the effect of CAFs on NSCLC. CAFs and normal fibroblasts (NFs) were isolated and identified. CAFs or NFs were cocultured with NSCLCs cells. Cell invasion and migration, and expression of E-cadherin, N-cadherin, SDF-1, CXCR4 and Xist were measured. SDF-1/CXCR4 axis inhibitor ADM3100 or low expression of Xist was added to verify the invasion and metastasis of NSCLC. The binding relationships of Xist, miR-15a-5p and MMP3 were analyzed. The effect of miR-15a-5p overexpression on H1299 was evaluated. Finally, lung metastasis experiment was carried out in vivo. CAFs promoted the invasion and EMT of NSCLC cells by secreting SDF-1. CAFs increased CXCR4 and Xist expressions in NSCLC cells. SDF-1 knockdown or ADM3100 decreased CXCR4 and Xist expressions. Silencing Xist reduced the promotion of CAFs on NSCLC. Xist targeted miR-15a-5p to regulate MMP3. Overexpression of miR-15a-5p promoted the invasion and EMT of NSCLC cells. CAFs caused more metastatic nodules and elevated SDF-1, CXCR4, MMP3 and XIST levels, and lowered miR-15a-5p level. Collectively, SDF-1 secreted by CAFs promotes lncRNA Xist through CXCR4, and Xist targets miR-15a-5p to regulate MMP3, thus promoting invasion and metastasis of NSCLC.

MSCs and CAFs interactions in the prostate and bladder cancer microenvironment as the potential cause of tumour progression

“…As in the case of MSCs, the influence of CAFs on the SDF-1/CXCR4 signalling pathway has recently been extensively studied. Recent studies show a significant influence of CAFs on this pathway, which interplay to among others, invasiveness and metastasis of NSCLC or progression of endometrial cancer [42,43]. Wang et al already in 2008, indicated that this pathway may be a promising therapeutic target, in their research they showed that the overall survival time of patients with positive CXCR4 in pancreatic cancer was lower than that of patients without this marker [44].…”