Table 1.
Paracrine and autocrine interactions between CAFs and CRC cells in relation to poor prognosis CRC subtype.
| Secretome/Mediator | Expression | Influence on Carcinogenesis | Ref. | |
|---|---|---|---|---|
| Chemokine | CCL2; CCL8 | Up | Secreted CCL2 and CCL8 from CAFs induce proliferation and invasion of CRC cells | [67] |
| CXCL14 | Up | Stimulates CAF pro-tumourigenic activity via autocrine effects on CAFs and paracrine signalling on neoplastic cells, leading to higher cancer cell proliferation | [68] | |
| IL-6/IL-11 | Up | Induce tumour proliferation and CAF formation | [69] | |
| STAT3 activation facilitated by IL-6/IL-11 in CAFs drives CRC progression and is associated with poor prognosis | [70] | |||
| Intrinsic STAT3 activity in CAFs induces the release of IL-6, TGF-β and VEGF by CRC cells and promotes carcinogenesis, immune suppression and metastasis | [71] | |||
| CXCR4/CXCL12 | Up | CXCR4/TGF-β1 axis supports the differentiation from HSCs into CAFs and promotes metastasis | [72] | |
| Growth factor | TGF-β | Up | TGF-β activity on CAFs promotes colonisation of CRC cells. TGF-β-stimulated CAFs secrete IL-11, which induces STAT3 signalling that supports cancer metastasis | [73] |
| Decreases T-cell activity, leading to cancer immune evasion | [74] | |||
| Presence of upstream transcription factors, SMADs, which predict the failure of immune checkpoint (PD-1) blockade | [75] | |||
| Secreted by CRC cells, interacts with CAF-derived exosome miR-17-5p, resulting in tumour invasion and metastasis | [76] | |||
| IGF-1/IGF-1R | Up | IGFBP7 (TGF-β-target gene) promotes cancer cell proliferation through tumour-stroma paracrine signalling | [77] | |
| IGF-1 and STAT3 drive CRC progression through cell autonomous and pro-tumourigenic activity of CAFs | [78] | |||
| Wnt/β-catenin | Up | Induce tumour invasion and metastasis | [79] | |
| CAF-derived WNT2 induces angiogenesis and promotes carcinogenesis | [80] | |||
| MicroRNA | miR-135b-5p | Up | Upregulation of miR-135b-5p by CAF-derived exosomes to support CRC cell growth and angiogenesis via TXNIP inhibition | [81] |
| ECM components | ADAMs | Up | ADAMs expressed by CAFs drive tumour invasion and metastasis | [82] |
| TIMP-1 | High expression of TIMP-1 stimulates stromal cells growth and activation of ERK1/2 kinase | [83] | ||
ADAMs: disintegrin and metalloproteinases; CCL2/8: chemokine (C-C motif) ligand 2/8; CXCL14: chemokine (C-X-C motif) ligand 14; IL-6/IL-11: interleukin 6/interleukin 11; TGF-β: transforming growth factor-beta; IGF: insulin growth factor; miR-135b-5p: microRNA135b-5p; TXNIP: thioredoxin-interacting protein; VEGF: vascular endothelial growth factor.