Table 3 Roles of TAM-derived cytokines in gynecological and breast cancers
Cytokines | Tumor type | Interacting molecules | Function | References |
|---|---|---|---|---|
IL-6 | Cervical cancer | IL-6/JAK/STAT3 | HPV E6 oncoprotein participates in the phosphorylation activation of the STAT pathway by IL-6 and promotes cancer cell proliferation | [84] |
| Â | ER-positive breast cancer | Â | The IL6/STAT3 pathway independent of ER pathway promotes the proliferation of cancer cells | [86] |
IL-1 | Breast cancer | sCD44 | A novel positive feedback loop between IL1β and CD44 promotes TNBC malignant progression | [75] |
IGF-1 | Breast cancer | Akt | Serum IGF-1 concentrations and IGF-I/IGFBP3 ratio correlated with Akt phosphorylation which promote breast cancer progression and poor disease outcome | [77] |
CXCL8/IL-8 | Endometrial carcinoma | HOXB13 | Down-regulation of ERα expression in endometrial carcinoma, leading to tumor invasion and poor prognosis | [88] |
|  | ER-positive breast cancer | HOXB13, mTOR | Up-regulation of HOXB13 can promote cell proliferation and metastasis in vitro and in vivo by directly inhibiting ERα, while ERα can be inhibited by decreasing the expression of mTOR | [89] |
|  | Epithelial ovarian cancer | Estrogen, IL-6 | Estrogen, IL-6 and CXCL8 interact to regulate epithelial ovarian cancer growth through a cascade of amplification effects of ERα pathway | |
VEGF-C/D | Endometrial cancer and cervical cancer | VEGFR-3 | VEGF-C, VEGF-D and receptor VEGFR-3 are correlated with different stages of tumor progression | |
EGF | Ovarian cancer | VEGF | EGFR activation and up-regulation of VEGF/VEGFR signaling pathway in surrounding tumor cells supported tumor cell proliferation and migration. EGF up-regulated αMβ2 integrin and ICAM-1 and promoted the adhesion of tumor cells to TAMs | [99] |
MMP-9 | ER-positive breast cancer | ER | TAMs secretion of MMP-9 is associated with reduced overall survival via ER | [104] |
MMP-7 | Ovarian cancer | p38 | MMP-7 promoted macrophage infiltration to further form tumor microenvironment | [105] |
uPA | Breast ductal carcinoma in situ | uPAR | uPA reshaped the extracellular matrix by degrading the components involved, which in turn led to the removal of tumor cells from the primary site | [110] |
TNF-α | Breast cancer | Estrogen | TNF-α involved in EMT and metastasis of breast cancer cells | [76] |
IL-10 | Cervical cancer | HPV E2 T cell | HPV E2 protein could bind to IL-10 gene promoter, triggering the increase in IL-10. Increased IL-10 inhibited T cell immunity | |
| Â | Breast cancer | CD8+ T cell | Macrophage-derived IL-10 overexpression leads to tumor development in response to CD8+ T cell-dependent chemotherapy | |
TGF-β1 | Cervical cancer | HPV E6/E7 | As tumors develop, TGF-β induces EMT | [118] |
|  | High-grade serous ovarian cancer | Unknown | High levels of TGF-β1 secretion promote peritoneal metastasis of cancer cells | [112] |
GDF15 | Cervical cancer | PI3K/AKT and MAPK/ERK | The PI3K/AKT and MAPK/ERK signaling pathways are phosphorylated by ErbB2 to promote tumor progression | [113] |