Identifiers
HUGO:CCL2
Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / CYTOKINES_CHEMOKINES_PRODUCTION
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / RECRUITMENT_OF_IMMUNE_CELLS
References
CASCADE:PLAU
PMID:27216177
FAP as a persistent activator of fibroblastic STAT3 through a uPAR-dependent FAK-Src-JAK2 signaling pathway.
STAT3 inducec CLL2 expression downstream of this signaling. CCL2 derived from FAP+CAFs mediates their ability to promote tumor growth and MDSC infiltration
CCL2 (MCP1)
CAF express MCP-1/CCL2 when co-cultured with cancer cells [48] and [49]. Galectin-1 expression, which was shown to regulate CAF activation, also controls MCP-1 expression in the activated cells and MCP-1 in turn facilitates tumour invasion and metastasis.
Although the mechanism of action described in the paper concentrated on the effects of MCP-1 on tumour cells, there is also a large body of evidence describing MCP-1's involvement in the recruitment of CCR2-positive immune cells such as monocytes, macrophages, dendritic cells and T cells. In 4T1 tumour bearing mice in which the Mcp-1 gene was deleted, a significant decrease of F4/80 positive macrophages was observed in the tumours
PMID:23527025
The primary tumors of MCP-1(-/-) mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1(-/-) mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation.
PMID:23943801
TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model.
PMID:24531940
Cancer-associated fibroblasts (CAFs) have been described to play critical roles in initiation, progression and metastasis of various cancers. However, the involvement of CAFs in oral cancer (OC) has not been well addressed. In this study, we demonstrate that CAFs, when cocultured with OC cells (OCCs), produce high levels of chemokine (C-C motif) ligand 2 (CCL2) and, subsequently, enhance endogenous reactive oxygen species production in cells. Oxidative stress stimulates expression of cell cycle progression proteins in OCCs, leading to promotion of OCC proliferation, migration, invasion and, OC tumor growth. On the other hand, oxidative stress triggered the activation of nuclear factor-kappaB (NF-??B) and STAT3 in CAFs, resulting in accelerating CCL2 expression.
PMID:23567181
CCL2, synthesized by both tumor cells and by CAFs, is a known chemoattractant of inflammatory monocytes, which express its receptor???CCR2
CCL5/RANTES and CCL2 secreted by CAFs isolated from human melanoma, breast and colon cancers mediated recruitment of Th17 cells from peripheral blood
PMID:19915063
Phosphorylated STAT1??is critical for IFN-gamma-induced (CCL2)MCP-1 production
PMID:17681149
PPARG participates in inhibition of secretion of proinflammatory molecules, such as CCL-3, TNF, and MCP-1 (CCL-2).
References
in_re571( Innate Immunity ):
PMID:17681149
PPARG participates in inhibition of secretion of proinflammatory molecules, such as CCL-3, TNF, and MCP-1 (CCL-2).
PMID:23508573
HMGB1 induces secretion of CCL2, CCL3 and CXCL10 (IP-10) via TLR4 pathway.
PMID:19915063
Phosphorylated STAT1??is critical for IFN-gamma-induced (CCL2)MCP-1 production.
→ CCL2@default
+ CCL2@default → CCL2:CCR2@INNATE_IMMUNE_CELL_Membrane
→ RECRUITMENT_OF_IMMUNE_CELLS@INNATE_IMMUNE_CELL_Cytosol
→ CCL2@INNATE_IMMUNE_CELL_Cytosol