Table 4 MSC promotion effects in cancers

Brain cancer

 Human bone marrow from ScienCell Research Laboratories

CD73⁺ CD90⁺ CD105⁺

tumor-like phenotype transformation

Glioma cell-derived exosomes, upregulating the levels of

Glut-1, HK-2, and PKM-2, activating glycolysis in MSCs

[125]

 Human bone marrow of healthy donor

SH2⁺ SH3⁺ CD29⁺ CD44⁺ CD71⁺ CD90⁺ CD106⁺ CD120a⁺ CD124⁺ CD14⁻ CD34⁻ CD45⁻

Increased tumor metastasis

SDF-1/CXCR4 and SDF-1/CXCR7 signaling

[124]

 Human adipose tissue from trochanteric fat of healthy donor

CD73⁺ CD90⁺ CD105⁺ CD45⁻

Increased tumor cell proliferation

MSC-EV

[281]

 Human adipose tissue

CD31⁻ CD45⁻

Increased tumor growth

Higher mRNA expression levels of angiogenic factors (VEGF, Ang-1, PDGF, and IGF) and SDF-1(CXCL12) in MSCs

[148]

 Mouse adipose tissue

Not stated

Increased tumor migratory capacity

MSC-secreted conditioned medium increases vimentin, MMP2, and NRAS expression

[282]

 Human adipose tissue from individuals receiving abdominoplasty

CD44⁺ CD90⁺ CD34⁻

Increased tumor growth; decreased apoptosis and H₂O₂-induced cancer cell death

Co-injection in vivo

Co-culture or MSCs-CM

[154]

 Human adipose tissue of individuals receiving abdominoplasty or mammoplasty

CD44⁺ CD105⁺ CD14⁻ CD34⁻ CD45⁻

Increased cancer cell migration; no significant effect on cancer cell proliferation, TMZ response, CSC traits

MSCs-CM

[282]

 Human umbilical cord Wharton's jelly (human umbilical cord perivascular cells)

Sh2⁺ SH3⁺ Thy-1⁺ CD44⁺ CD34⁻ CD45⁻

Increased tumor growth and migration; no significant effect on TMZ response

Cytokines from MSCs-CM (ex. CCL2, PDGF-C, Sema-7A, periostin, IL6)

[162]

 Human umbilical cord blood of healthy donors

CD29 CD44 CD73 CD90 CD105 CD166

Increased tumor growth

Exosomes

CD133⁺ GBM secreted MCP-1/CCL2 and SDF-1/CXCL12 induce migration of MSCs

[160]

Lung cancer

 Human bone marrow

Not stated

Increased tumor growth, cancer cell proliferation, intra-tumoral angiogenesis and M2 polarization of macrophages

Downregulated PTEN,

PDCD4 and RECK gene expression in cancer cells largely through miR-21-5p, which derived from EVs of MSCs pre-challenged with hypoxia

[126]

 Human adipose tissue stem cell line

Not stated

Increased migration capacity

ADMSC-differentiated CAFs promoted cancer EMT by NOTCH pathway

[149]

 Human umbilical cord of healthy donor

CD133⁺ CD271⁺ CD105⁺ CD3⁻ CD14⁻ CD19⁻ CD38⁻ CD66b⁻

Increased tumor EMT, invasion, and migration; decreased tumor proliferation and increased tumor apoptosis

Exosomes derived from MSCs activated Smad2/3, Akt/GSK-3β/β-catenin, NF-kB, ERK, JNK, and p38 MAPK signaling pathway by TGF-β1

[159]

 Human umbilical cord of healthy donor

CD105 CD73 CD90 CD45 CD34 CD14 CD19 HLA-DR

Increased tumor cell proliferation and decreased tumor cell apoptosis

Reduced PTEN expression mediated by the MSC-EV-transmitted miR-410

[158]

 Human umbilical cord Wharton's jelly

CD105⁺ CD90⁺ CD166⁺ CD73⁺ CD45⁻ CD31⁻ CD34⁻

Increased AC-LCSC tumor cell proliferation and expression of CSC markers (ALDH⁺ and CD133⁺ cell population)

MSC-CM and in vivo co-transplantation

[161]

Liver cancer

 Human bone marrow MSC cell line

CD44⁺ CD90⁺

Increased tumor progression, but decreased pulmonary metastasis

Decreased TGFβ1 and MMP2 expression in cancer cells

[165]

 Human bone marrow from patients with orthopedic surgery

CD44⁺ CD73⁺ CD90⁺ CD105⁺ CD146⁺ CD34⁻ CD45⁻

Increased tumor growth, migration and invasion

MSC-dependent activation of the CXCR4, PI3K/Akt, Ras/Erk pathways

[127]

 Human bone marrow from ATCC

Not stated

Increased tumor growth and metastasis

Activated pERK signaling pathway and over-expressed integrin α5 in HCC; decreased NK cell marker CD56 and increased IL-6 and TNF-α in tumor niche

[128]

Colorectal cancer

 Human bone marrow of healthy donor

CD29⁺ CD44⁺ CD73⁺ CD90⁺ CD105⁺ CD166⁺ MHC-DR⁺ CD14⁻ CD34⁻ Flk-1⁻

Increased tumor growth

MSC-differentiated CAFs expressed PDGFR to mediate tumor growth and metastasis

[130]

 Human bone marrow of healthy donor

CD29⁺ CD44⁺ CD73⁺ CD90⁺ CD105⁺ CD166⁺ MHC-DR⁺ CD14⁻ CD34⁻ Flk-1⁻

Increased tumor growth, angiogenesis, and metastasis

MSC-differentiated into CAFs; paracrine effects of MSCs;

[129]

 Human bone marrow of healthy donor

CD73⁺ CD90⁺ CD105⁺ CD34⁻ CD45⁻

Increased migration capacity

MSC-secreted PAI-1 promoted cancer cell migration

[134]

 Human bone marrow of healthy donor

CD29⁺ CD44⁺ CD73⁺ CD90⁺ CD105⁺ CD166⁺

Increased tumor-initiating ability and tumor growth

MSC-secreted IL6 increased cancer cell CD133 expression by activation of JAK2/STAT3

[132]

 Human bone marrow from sternum of healthy donor

CD49c⁺ CD73⁺ CD90⁺ CD105⁺ CD34⁻ CD45⁻ CD184⁻ CD106⁻

Increased tumor growth, invasion; decreased survival

MSC-secreted NRG1 activated HER2/HER3-dependent PI3K/AKT pathway

[135]

 Human bone marrow from iliac crest of healthy donor

Not stated

Increased tumor growth and angiogenesis

MSC-secreted IL6 induced ET1/AKT or ERK pathway in endothelial cells to promote angiogenesis

[133]

 Human bone marrow from the iliac crest of the patient following bone defect reconstruction

Not stated

Increased tumor growth, cell proliferation, invasion and cancer stemness-related properties

Suppressed RNA-binding protein PTBP1 by indirect co-culture with MSCs

[136]

 Human bone marrow from the femoral head during hip-replacement surgery

Not stated

Increased cancer cells stem cell-like traits

MiR-142-3p contained in exosomes derived from MSCs promoted the Notch signalling pathway by downregulating Numb in cancer cells

[136]

 Human bone marrow from ATCC

Not stated

Increased tumor cell proliferation, EMT, migration, and invasion

TNF-α-primed-MSCs secreted high level of CCL5 which further involved cancer cells’ CCl5/CCR1/β-catenin/Slug signaling pathway

[137]

Renal cancer

 Human umbilical cord Wharton's jelly of healthy donor

Not stated

Increased tumor growth

Induction of HGF synthesis via RNA transferred by MSC-MVs activated AKT and ERK1/2 signaling

[163]

 Human adipose tissue from liposuction

CD44⁺ CD90⁺ CD34⁻ CD45⁻

Increased Ciprofloxacin resistance

Not explored

[151]

 Human amniotic fluid from healthy pregnant women

CD44⁺ CD90⁺ CD34⁻ CD45⁻

Increased Ciprofloxacin resistance

Not explored

[151]

Ovarian cancer

 Healthy human donor

CD90 CD105 CD106 CD117 CD146 CD56 CD166 CD29 CD44 CD14 CD31 CD34 HLA-DR

Increased tumor growth and angiogenesis

LL-37 recruited MSCs, which release trophic factors that initiate angiogenesis and/or differentiate into blood vessel-supporting cells

[153]

 Human adipose tissue from omentum of normal donors

CD105⁺ CD73⁺ CD90⁺ CD34⁻

Increased tumor growth and metastasis

Elevated the expression of MMP2 and MMP9

[152]

Endometrial cancer

 Human adipose tissue from omentum of patient with recurrent adenocarcinoma of endometrium and ovary

CD44⁺ CD29⁺ CD90⁺ CD105⁺ CD34⁻ CD45⁻ CD11b⁻

Increased tumor growth and cell proliferation

Not explored

[283]

Breast cancer

 Human bone marrow of healthy donor

Not stated

Increased tumor metastasis

MSCs involve in driving recruitment of TAMs and MDSCs

[143]

 Human bone marrow of healthy donor

Not stated

Increased skin invasion and metastasis

Activation of EGFR signaling pathway

[284]

 Human bone marrow of healthy donor

Not stated

Increased tumor cell migration and invasion

Tumor and stroma physical interactions activated Notch1 by TNFα or IL-1β, which further lead to CXCL8 production

[144]

 Human bone marrow from Lonza

CD29⁺ CD44⁺ CD105⁺ CD166⁺ CD90⁺ CD73⁺

CD14⁻ CD34⁻ CD45⁻HLA-DR⁻ CD19⁻

Increased tumor lung metastases

Elevated CXCL8 (IL-8), CCL2 (MCP-1), and CCL5 (RANTES) by TNFα/IL-1β primed TNBC:MSC co-cultures

[144]

 Human bone marrow of healthy donor

CD105⁺ CD45⁻

Increased tumor motility, invasion and

metastasis

CCL5 secreted by MSCs activated CCL5-CCR5 signaling in cancer cells

[142]

 Human bone marrow of healthy donor

Not stated

Increased tumor growth and bone metastasis

Not explored

[285]

 Human bone marrow of healthy donor

Not stated

Acquisition of dormant phenotypes including decreased tumor cells proliferation, the abundance of stem cell–like surface markers, invasion capacity, and sensitivity to docetaxel

miR-23b contained in exosomes derived from MSCs

suppressed MARCKS expression

[145]

 Human adipose tissue from women (BMI > 30) undergoing liposuction from the subcutaneous abdominal adipose tissue

CD29 CD166 CD73

CD105 CD90 CD11b CD31 CD34 CD45 HLA-DR

Increased tumor growth and angiogenesis

CXCL1/8 secreted by MSCs activated CXCL1/8-CXCR1/2 signaling in cancer cells

[150]

 Human adipose tissue from patients undergoing tumescent liposuction

CD44⁺ CD105⁺ HLA-ABC⁺ CD29⁺ Fik1⁺

CD45⁻ CD31⁻ CD34⁻ CD106⁻ CD184⁻

Increased tumor cell migration

Exosomes derived from MSCs activated Wnt signaling pathway

[155]

 Human adipose tissue from ScienCell Research Laboratories (Carlsbad, CA)

CD73⁺ CD90⁺ CD105⁺

Increased Doxorubicin resistance

MSC-secreted conditioned medium promoted BCRP protein expression in cancer cells

[156]

 Human adipose tissue from liposuction

CD73⁺ CD90⁺ CD105⁺ CD34⁻

Increased tumor metastatic spread

MSC dose dependent

[286]

 Human umbilical cord of healthy donor

Not stated

Increased tumor cell invasion and metastasis

IL-8 and IL-6 secreted by MSCs activated the autocrine IL-8

and IL-6 signaling in cancer cells and induced CD44 + /CD24 − cells

[286]

 Human umbilical cord of healthy donors

CD29⁺ CD44⁺ CD90⁺ CD34⁻ HLA-DR⁻

Increased tumor cells proliferation and migration

MSC-CM inhibited E-cadherin expression, increased the expression of N-cadherin, ZEB1 and PCNA through activation of the ERK pathway

[157]

Prostate cancer

 Mouse bone marrow from femurs

CD90⁺ CD34⁻/CD45⁻

Increased tumor cell migration and invasion

SDF1a secreted by MSCs

[123]

Melanoma

 Resident MSCs of bone and liver

Not stated

Increased tumor metastasis to bone and liver

MCC interact with resident MSCs at the perivascular space through co-expressed CD146 and CXCL12-CXCR4 signaling

[287]

Bone cancer

 Human bone marrow from the proximal femur during orthopedic surgery

Not stated

Increased tumor growth and metastasis to lung

MSC-secreted IL6 activated tumor STAT3 signaling pathway

[139]

 Human bone marrow from patients with orthopedic surgery

CD44⁺ CD73⁺ CD90⁺ CD105⁺ CD146⁺ CD34⁻ CD45⁻

Increased tumor growth, migration and invasion

MSCs-dependent activation of the CXCR4, PI3K/Akt, Ras/Erk pathways

[127]

 Human bone marrow

CD29⁺ CD44⁺ CD105⁺

CD45⁻ HLA-DR⁻

Increased tumor cell growth

Activation of Hedgehog signaling pathway by MSC-derived exosomes

[138]

 Human bone marrow from TaKaRa Biotechnology

Not stated

Increased tumor cell growth and metastasis

Paracrine effect of IL-8 through activation of FAK pathway

[140]

 Human bone marrow of healthy donor

CD73⁺ CD90⁺ CD105⁺

CD34⁻ CD45⁻ CD19⁻ CD14⁻

Increased tumor cell invasion and transendothelial migration

MSCs trans-differentiate into CAFs, increasing GRO-a, MCP-1, IL-6 and IL-8 levels in the tumor microenvironment

[141]

 Human bone marrow

CD73⁺ CD90⁺ CD105⁺

CD34⁻ CD45⁻ CD3⁻

Increased tumor cell proliferation

Not explored

[288]

Gastric cancer

 Human bone marrow

CD29⁺ CD44⁺ CD105⁺

CD45⁻ HLA-DR⁻

Increased tumor cell growth

Activation of Hedgehog signaling pathway by MSC-derived exosomes

[138]

 Human bone marrow from ATCC

Not stated

Increased tumor cells viability and invasion

MSCs recruitment and presence of CAF-like myofibroblastic phenotypes by tumor-derived HDGF

[131]

Head and neck cancer

 Human bone marrow from patients during hip-replacement surgery

CD73 + CD90 + CD105 + CD19- CD34-

Increased tumor cell invasion

Induction of ALP and MMP9 activity

[146]

Esophageal cancer

 Human bone marrow

CD29⁺ CD44⁺ CD73⁺ CD90⁺ CD45⁻ CD31⁻

Increased tumor cell proliferation, viability and invasion

Gremlin1 derived from MSC-CM is related to TGF-β/BMP signaling pathway

[147]

Bladder cancer

 Human adipose tissue from liposuction

CD44⁺ CD90⁺ CD34⁻ CD45⁻

Increased Ciprofloxacin resistance

Not explored

[151]

 Human amniotic fluid from healthy pregnant women

CD44⁺ CD90⁺ CD34⁻ CD45⁻

Increased Ciprofloxacin resistance

Not explored

[151]