Copyright
©The Author(s) 2022.
World J Gastroenterol. Jul 14, 2022; 28(26): 3027-3046
Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3027
Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3027
Table 1 Factors secreted by the tumor microenvironment and their role in colorectal cancer progression
Released/secreted components | Source, TME cell | Known effects in CRC | Ref. |
Growth factors | |||
TGF-β | CAFs; TIICs1; MSCs1 | Proliferation on tumor and stromal cells in late stages of tumorigenesis. EMT program and CSC-like traits. Metastasis, vasculogenesis and angiogenesis | [5,21,136] |
BMPs | CAFs | Anti-tumor activity. Or pro-tumor activity, induce CSCs phenotype, EMT program and chemoresistance. Differentiation of colon CSCs | [5,137,138] |
HGF | CAFs; TIICs; MSCs1 | Invasion, metastasis and stemness | [21,54,139,140] |
VEGF | ECs; CAFs; TIICs | Angiogenesis, invasiveness, metastasis | [104,140,141] |
FGF | CAFs; MSCs | CAFs profiles. Tumor growth and metastasis | [142,143] |
PDGF | CAFs | Tumor growth and metastasis | [144] |
TNF-α | TIICs | Proliferation. Growth arrest and cancer cell death, angiogenesis and metastasis | [141,145] |
Cytokines | |||
IL-1 | TIICs | Angiogenesis and metastasis | [141,146] |
IL-2 | TIICs | Anti-tumor activity | [1,147] |
IL-6 | TIICs; MSCs; CAFs | Proliferation, angiogenesis and metastasis | [1,141] |
IL-8 | TIICs; MSCs | Tumor growth, angiogenesis and chemoresistance | [1,148] |
IL-17 | CAFs; TIICs | Anti-tumor or pro-tumor activity. Invasion and self-renewal of CSCs | [1,104,149] |
IL-18 | TIICs | Anti-tumor activity | [150] |
IL-22 | TIICs | Proliferation, invasion and stemness | [1,104] |
IL-33 | ECs; TIICs | Anti-tumor activity Suppresses tumorigenesis. Or pro-tumor activity. Angiogenesis and metastasis. Tumor growth through immunosuppressive microenvironment favoring | [1,104,151] |
CCL2 | TIICs; MCS | Tumor progression | [152] |
CCL5 | TIICs | Tumor progression. Acts on tumor cells and TAMs | [153] |
CCL7 | CAFs | Proliferation, invasion, and migration | [154] |
CXCL12 | CAFs; MSCs | Proliferation and invasion | [142,155] |
PTHrP | Undefined TME cells | Proliferation, invasion, angiogenesis, migration and chemoresistance | [34,35,66,156,157] |
Osteopontin | TIICs | Metastasis, stemness and chemoresistance | [85] |
Prostaglandins | |||
PGs (like PGE2) | CAFs; TIICs; MSCs | Resistance to apoptosis, increased proliferation, angiogenesis and metastasis | [21,32] |
Signaling pathways ligands | |||
NOTCH ligands (Jagged-1; Jagged-2; DLL4) | ECs | CSCs phenotype, EMT program and metastasis | [104,158] |
WNT ligands (Wnt2, Wnt5) | CAFs | Invasion, metastasis and angiogenesis | [44,45,54] |
Enzymes | |||
Serine proteinases (like MMPs) | TAMs; TANs | Invasion and angiogenesis | [140,145] |
Immunosuppressive enzymes (like iNOS) | TIICs | Tumor progression. Inhibitory effect on the immune system, apoptosis of immune cells | [39] |
Receptors | |||
TLRs | CAFs, ECs | Inflammatory-mediated tumorigenesis | [41,43] |
RNA molecules | |||
miR-92a-3p | CAFs | CSCs phenotype, EMT program and chemoresistance | [24] |
lncRNA H19 | CAFs | Stemness and chemoresistance | [25] |
miR-155 | MSCs1 | Migration | [21,159] |
miR-375 | MSCs1 | Chemoresistance | [21,160] |
cRNA | CAFs | Tumor progression or anti-tumor activity | [26,27] |
- Citation: Novoa Díaz MB, Martín MJ, Gentili C. Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance. World J Gastroenterol 2022; 28(26): 3027-3046
- URL: https://www.wjgnet.com/1007-9327/full/v28/i26/3027.htm
- DOI: https://dx.doi.org/10.3748/wjg.v28.i26.3027