Table 1 Key tumor microenvironmental components, stemness factors and their functions in CSCs maintenance
S.No. | TME Stemness factors | Cancer/cells | Functions | References |
|---|---|---|---|---|
1. | Interleukin 8 | Breast Cancer | It promoted the EMT and acquisition of stemness in MCF-7 cells | [35] |
2. | Platelet-activating factor (PAF) | Ovarian cancer | It endorsed progression and chemoresistance of ovarian cancer via PAF/PAF-R inflammatory pathway. | [36] |
3. | YY1 | Lung cancer | It stabilized HIF-1α protein through YY1/HIF-1α axis promotes stemness in lung cancer cells | [37] |
4. | Mitochondrial ribosomal protein S18-2 | Mouse fibroblasts | It positively correlated with KLF4 to enhance stemness in primary mouse embryonic fibroblasts. | [38] |
5. | Monoamine oxidase A | Prostate cancer | It induced the IL-6 transcription through Twist1/IL-6/STAT3 pathway | [39] |
6. | Chemokine (C-C motif) ligand 8 (CCL8) | GBM | It activated the ERK1/2 phosphorylation to mediate stemness. | [40] |
7. | IL-10 | Non-small cell lung cancer (NSCLC) | It promoted through JAK1/STAT1/NF-κB/Notch1 signaling to maintain CSCs-like cells | [41] |
8. | HGF and IL6 | Hepatocellular carcinoma (HCC) | It secreted from CAFs promoted the stemness through phosphorylation of STAT3 | [42] |
9. | CCL2 | esophageal cancer | It is derived from tumor-associated macrophages to enhances the stemness | [43] |
10. | Phospholipase D2 (PLD2) | colon cancer | It induced senescence in nearby fibroblasts leads to senescence-associated secretory phenotype to promotes stemness | [44] |
11. | BMP4 | oral cancer | It is derived from CAFs and regulated the self-renewal. | [45] |
12. | Osteopontin | colon cancer | It is derived from CAFs and drives in situ clonogenicity | [18] |
13. | Exosomal lncRNA H19 | colorectal cancer | It is fostered the stemness and chemoresistance to activate β- catenin pathway | [46] |
14. | rhIL-8 | Ovarian cancer | It promoted M2 macrophage polarization and stemness in SKOV3 cells | [47] |
15. | CD10 GPR77 | Breast cancer | It activated NFκB via p65 phosphorylation and acetylation to promote tumor formation and stemness. | [19] |
16. | Interleukin 7-producing fibroblasts | Breast cancer | It modulated CXCL12/CXCR4 axis to enhance breast tumor cell stemness | [48] |
17. | CD4 + CD25 + Tregs | Breast cancer | It activated NFκB-CCL1 signaling, to promotes the stemness in breast cancer cells. | [49] |
18. | High-mobility group box 1 (HMGB1) | Breast cancer | It activated the HMGB1-TLR4 axis to maintain stemness in luminal breast cancer cells. | [50] |
19. | Sp1 | Glioblastoma | It acted as critical transcriptional factor to maintain stemness in GBM cells | [51] |
20. | Specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) | Hepatocellular carcinoma | It enhanced the desumoylation of HIF-1α to promotes the stemness in HCC cells | [52] |
21. | IL33 | Colon Cancer | It expressed in vascular endothelial cells of colon cancer TME and induced JNK phosphorylation to promote expression of stem cell genes. | [53] |
22. | IL-6 | Osteosarcoma | It derived from mesenchymal stromal cells and promotes the osteosarcoma Stemness | [54] |
23. | MUC1 | Lung Cancer | It promoted the tumor-associated macrophages-mediated lung cancer stemness | [55] |
24. | BCLXL | Colorectal Cancer | It derived from human colonic fibroblasts and regulated stemness in colon cancer cells | [56] |
25. | ILs-3, 6 and 11 | Prostate cancer | It promoted the stemness markers SOX2, CD44 and ABCG2 expression in prostate cancer cell lines | [57] |
26. | Laminins | Glioma | It promoted the stemness in 3D model of glioma cells | [58] |
27. | Microsomal PGE synthase-1 (mPGES-1) | Prostate cancer | mPGES-1 expressed prostate cancer cells showed stem-cell-like features to promote the CD44, Nanog and Oct4 levels. | [59] |
28. | Glioma-associated-human MSCs | Glioma | It derived from stromal component of gliomas to increase the self-renewal potential in glioma cells | [60] |
29. | Endothelial cells Endothelial Jagged1 | Breast cancer | It promoted the enrichment of CD44 cells population and specifically endothelial Jagged1 enhance the notch signaling in breast cancer cell lines | [61] |
30. | Interleukin-22 (IL-22) CD4(+) T cells | Colorectal cancer | It activated the STAT3 and histone 3 lysine 79 (H3K79) methyltransferases (DOT1L) and induced stemness via NANOG, SOX2 and Pou5F1 in colorectal cancer | [62] |
31. | α6β1 integrin | Breast cancer | It was expressed in CD44 (high)/CD24(low) epithelial and mesenchymal population and controlled by VEGF signaling determine the breast cancer stem cell fate. | [63] |
32. | IGF2 | NSCLC | It derived from CAFs and induced the Nanog expression to promote stemness in NSCLC. | [17] |
33. | Myeloid cells | Pancreatic cancer | It activated STAT3 and increase the ALDH1 positive population. | [64] |
34. | CD44 | Melanoma | It expressed in CAFs on hypoxic and hypo nutritional conditions in melanoma cells | [65] |
35. | High-density mammary fibroblasts | Breast cancer | It involved JNK1 and TGF-β signaling to promotes stemness | [66] |
36. | TGF-β | Gastric Cancer | It derived from CAFs and regulate the stemness in gastric cancer cells. | [67] |
37. | Myeloid-derived suppressor cells (MDSCs) | Ovarian carcinoma | It targeted the miRNA101-CtBP2 axis to enhance stemness gene expressions. | [68] |