CXCL12, also known as stromal-derived-factor-1 (SDF-1), is a homeostatic chemokine. It plays essential roles in regulating physiological and pathological processes such as embryogenesis, hematopoiesis, angiogenesis, and inflammation. CXCL12 exerts its functions mainly by interacting with its receptors CXCR4 and CXCR7, activating multiple signaling pathways like ERK1/2, ras, p38 MAPK, PLC/MAPK, and SAPK/JNK [3,4,5,6,8].

In fibrosis, accumulated evidence shows that the CXCL12/CXCR4 axis is involved in multiple pathological mechanisms such as inflammation, immunity, epithelial-mesenchymal transition, and angiogenesis, and can improve fibrosis levels in organs like the heart, liver, lung, and kidney, making it a promising target for anti-fibrotic therapy [1]. In cancer, the CXCL12-CXCR4/CXCR7 axis has a broad impact on tumor cell proliferation, survival, angiogenesis, metastasis, and the tumor microenvironment, participating in the onset and development of many cancers including leukemia, breast cancer, and colorectal cancer. For example, in bladder cancer, cancer-associated fibroblasts-derived CXCL12 promotes cancer cell migration, invasion, and upregulates PDL1, enhancing immune escape [2,5,7].

In conclusion, CXCL12 is a crucial chemokine in various biological and pathological processes. Studies, especially those using gene-based models (although not specifically detailed as KO/CKO mouse models in the given references), have revealed its significant roles in fibrosis and cancer. Understanding CXCL12's functions provides potential therapeutic targets for these diseases.