The Effects of Mesenchymal Stem Cell on Colorectal Cancer

Table 4

The effects of MSCs within the CRC microenvironment.

MSC-CRC interaction	Mode of function	Mechanisms	References
Inhibition	Cell-to-cell contact	Inhibiting the expression of proinflammatory cytokines and STAT3 activation	[133]
	Cell-to-cell contact	Induces apoptosis and interferes with tumor initiation through the dysregulation of Wnt and TGF-β-Smad signaling pathways	[134]
	Paracrine	miR-165-p overexpression in BM-MSC-exosomes inhibited the proliferation, migration, and invasion and promoted apoptosis of CRC cells by downregulating ITGA2 expression.	[135]
	Paracrine	miR-4461 in BM-MSC-exosomes inhibits the proliferation, migration, and invasion of CRC cells by reducing the expression of COPB2.	[136]
	Paracrine	MSC-exosome-derived miR-3940-5p inhibited CRC cell invasion, EMT, and metastasis by targeting ITGA6 and subsequent TGF-β1 inactivation.	[137]
	Paracrine	miR-15a carried by AD-MSC-EVs restricted CRC immune escape by downregulating the KDM4b/HOXC4/PD-L1 axis.	[138]
Promotion	Cell-to-cell contact	Regulating cell cycle and inhibiting apoptosis through the activation of NF-κB mediated by AMPK/mTOR	[143]
	Cell-to-cell contact	Promoting the progression of CRC cells through IL-6/JAK 2/STAT3 signal	[144]
	Cell-to-cell contact	The activation of JAK/STAT3 stimulated by the TGF-β1 or CXCR4/TGF-β1 axis can induce MSCs to differentiate into CAFs, which can promote the progression of CRC.	[66, 145, 152]
	Cell-to-cell contact	Interacting with CRC cells through CCL3/4/5 -CCR5 to promote the growth of CRC tumors in vivo	[148]
	Cell-to-cell contact	Promoting the EMT process of CRC through the CCL5/β-catenin/Slug pathway and SPARC	[147, 151]
	Cell-to-cell contact	Activating the HER2/HER3-dependent PI3K/Akt signaling cascade in CRC cells by releasing soluble NRG1.	[149]
	Cell-to-cell contact	Affecting the early xenograft growth of CRC cells with specific α-catenin deficiency by secreting extracellular matrix	[150]
	Cell-to-cell contact	Regulating the P53/P21 pathway through posttranscriptional regulation helps CRC resist senescence.	[153]
	Cell-to-cell contact	Promoting CRC angiogenesis through paracrine’s high levels of the proangiogenic factor IL-8	[154]
	Paracrine	miR-222 targets ATF3 and inhibits the transcriptional activity of AKT1, thereby promoting malignant invasion and immune escape of CRC cells.	[157]
Affection	Paracrine	Inducing morphological and functional changes in colon mesenchymal stem cells by secreting exosomes	[155]