Importance of CCL2-CCR2A/2B signaling for monocyte migration into spheroids of breast cancer-derived fibroblasts

From sentinel cells to inflammatory culprits: cancer‐associated fibroblasts in tumour‐related inflammation

“…Although the signals that recruit, 'educate', and activate CAFs to mediate tumour-promoting inflammation are complex and most likely tumour/organ type-specific, these studies collectively reveal that CAFs generating an inflammatory microenvironment originate from resident or recruited fibroblasts that are activated by paracrine signalling from initiated epithelia and/or immune cells. CAF signalling recruits myeloid cells CCL2, a known macrophage chemoattractant [62], was found to promote infiltration of blood monocytes into mammary CAF spheroids [63,64]. These observations were supported by in vivo data: in a mouse model of transplantable mammary carcinoma, CAF-secreted CCL2 recruited macrophages into mammary tumours and specific ablation of CCL2 reduced tumour metastasis [65].…”

Cancer-associated fibroblasts: A multifaceted driver of breast cancer progression

“…In this vein, mCAFs are also recognized as crucial players, as cytokines and chemokines secreted by them are well known as recruiters of immune cells in the tumor microenvironment [18,143]. Chemokine CCL2 synthesized by CAFs was found to promote infiltration of monocytes/macrophage into primary tumors and metastatic sites in vitro and in vivo, resulting in tumor growth, survival and distant metastasis in mouse models [144][145][146]. There are many other CAF-secreted inflammatory mediators such as IL-6, TNF, SDF-1, and CAFs are revealed to have the capability to recruit various immune cells including tumor associated macrophage, mast cells, and lymphocytes [18].…”

Molecular mechanism underlying the tumor-promoting functions of carcinoma-associated fibroblasts

“…Ellem et al have proved that estrogen-induced CAFs in prostate cancer produce CXCL12, which can recruit mast cells into tumor stroma in a CXCR4-dependent manner [72]; Ksiazkiewicz et al have also reported CCL2-CCR2A/2B pathway can promote infiltration of blood monocytes into mammary CAF areas [73]. In addition, the pro-inflammatory signature in CAFs is provided with the potential to modulate the functions of immune cells in the tumor microenvironment.…”