Table 1.
Role of inflammatory mediators in different stages of tumor progression.
| Inflammatory Mediators | Secreting Cell Type | Stages in Tumor Progression | |||
|---|---|---|---|---|---|
| Initiation and Progression | Angiogenesis | Metastasis | Chemoresistance | ||
| TNF-α ligands, TNFRI, TNFRII | OC cells, infiltrating monocytes, macrophages | ↑ autocrine production of TNF-α and IL-6, M-CSF, CXCL2, CCL2 [93,94] and AIDS mRNA level [90] | ↑ VEGF, VEGF↑ CXCL12 and promotes angiogenesis [139,140,141] | ↑ TGF-α secretion by stromal fibroblasts which promote peritoneal metastasis [148] Enhances migration of OC cells towards CXCL12 [149,150] | |
| IL-6 | Ovarian epithelial cells, OC cells, M2 macrophages, mesothelial cells, TAMS, ascites | ↑Proliferation by promoting G1 to S transition and MAPK-ERK- Akt activation and STAT3 activation [101,102] ↓IL-2, resulting in immune suppression [103] |
Induces STAT3 and MAPK phosphorylation which enhances migration of endothelial cells [143] sIL-6R-IL-6 facilitates angiogenesis in cells lacking IL-6 receptor [144] |
Stimulates production of MMPs in OCs which ↑ invasion and migration [101,104] ↑ IL-6 in ascites enhances invasion via JAK-STAT signaling [151] | ↓ Caspase- 3 cleavage and makes OC cells resistant to cisplatin and paclitaxel [152] ↑Expression of MDR1, GSTpi, Bcl-2, Bcl-xL, and XIAP [152] |
| IL-8 | Pre-ovulatory follicles, OC cells, ascites | ↑ Proliferation by ↑ cyclin B1 and cyclin D1 via pAkt [110] | ↑ Expression of VEGF, MMP-2, MMP-9 promoting angiogenesis [110] | Activates TAK1/ NF-κB via CXCR2 [153] | Blocks TRAIL induced apoptosis to promote resistance [154] |
| LPA | Follicular fluid, corpus luteum, OC cells, ascites | ↑ IL-6 and IL-8 via NF-κB and AP-1 [113,114,122] ↑COX-2 AND MMP2 [115,120,121] ↑ phosphorylation of Akt and ERK resulting in increased cell cycle [123,124] | ↑ Expression of VEGF via Myc and Sp-1 [155] | ↑ urokinase, which results in degradation of basemembrane protein to promote metastasis [156,157] | |
| Prostaglandins, COX-1 and COX-2 | Ovary, FT, uterus, MDSCs | ↑ CXCR4 and SDF1 in MDSCs resulting in immune suppression [128] | ↑ Bcl-2 and blood vessel formation [158,159] | ↑ Bcl-2, thus inhibiting apoptosis in lung, colon, breast and prostate cancers [158,159] | |
| TGF-β and EGF | OC cells, CAFs | TGF-β ↑ VCAN, which activates NF-κB and ↑MM-9 [160] | ↑ EGF protects cells from cisplatin-induced apoptosis [161]. Inhibiting TGF-β sensitizes resistant cells [162] | ||