Identifiers
C-X-C motif chemokine ligand 12
HUGO:CXCL12 hgnc_id:HGNC:10672 HGNC:10672 ENTREZ:6387 UNIPROT:P48061
HUGO:CXCL12
CASCADE:PGE2
CASCADE:CXCL12
Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / CYTOKINES_CHEMOKINES_PRODUCTION
Cancer Associated Fibroblasts / INFLAMMATORY_SIGNALING_PATHWAYS
Cancer Associated Fibroblasts / TREG_MODULATORS
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / RECRUITMENT_OF_IMMUNE_CELLS
References
CASCADE:CXCL12
CASCADE:TGFB
CASCADE:HGF
PMID:23034983
TGFB upregulates gene expression of CAF markers ,??FSP1 (S100A4), and??TNC. (provably via SMAD3), and gene expression of CCL5, SDF1(CXCL12), BMP4, IL6, CXCL7, IL6R, IL6ST, CXCL5
PMID:15882617
CAFs promote angiogenesis by recruiting endothelial progenitor cells (EPCs) into carcinomas, an effect mediated in part by SDF-1. CAF-secreted SDF-1 also stimulates tumor growth directly, acting through the cognate receptor, CXCR4, which is expressed by carcinoma cells. Our findings indicate that fibroblasts within invasive breast carcinomas contribute to tumor promotion in large part through the secretion of SDF-1.
PMID:23402812
Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer.
HGF induces expression markers of activated fibroblasts such as FAP, CXCL12 (SDF1),aplpha-SMA
PMID:15261139
The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion.
PMID:24277834
Three findings suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) explained the overriding immunosuppression by the FAP(+) cell: T cells were absent from regions of the tumor containing cancer cells, cancer cells were coated with the chemokine, CXCL12, and the FAP(+) CAF was the principal source of CXCL12 in the tumor. Administering AMD3100, a CXCL12 receptor chemokine (C-X-C motif) receptor 4 inhibitor, induced rapid T-cell accumulation among cancer cells and acted synergistically with ??-PD-L1 to greatly diminish cancer cells, which were identified by their loss of heterozygosity of Trp53 gene.
Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion.
PMID:20535745
CXCR4 receptor and CXCL12 both are expressed in fibroblasts and probably provides positive loop in fibroblast activation
PMID:23567181
CAF-mediated recruitment of T lymphocytes is facilitated by secretion of chemokines and cytokines that promote the recruitment of tumor-promoting T cells, including CXCL9, CXCL10, and CXCL12 (SDF-1??)
PMID:21521526
Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers
Our data show that in the setting of hypoxia and CXCR4 up-regulation in Treg, CXCL12 expression may have the negative consequence of enhancing Treg recruitment and suppressing the anti-tumour immune response.
PMID:20644254
CXCR4, the receptor for the chemokine CXCL12 (also known as SDF-1), also plays an important role in facilitating macrophage migration in vivo.
PMID:22025564
PGE(2) was essential both for expression of functional CXCR4 in cancer-associated MDSCs and for production of its ligand CXCL12 by tumor cells. Frequencies of CD11b(+)CD14(+)CD33(+)CXCR4(+) MDSCs closely correlated with CXCL12 and PGE(2) levels in patient ascites. MDSCs migrated toward ovarian cancer ascites in a CXCR4-dependent manner that required COX2 activity and autocrine PGE(2) production.
PMID:17035340
The secretion of HMGB1 is required for the migration of maturing dendritic cells.
myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12
→ CXCL12@default
→ RECRUITMENT_OF_IMMUNE_CELLS@INNATE_IMMUNE_CELL_Cytosol
+ CXCR4@INNATE_IMMUNE_CELL_Membrane → CXCL12:CXCR4@INNATE_IMMUNE_CELL_Membrane