Mesenchymal Stromal/Stem Cells in the Tumor Microenvironment and Their Role in Tumor Progression

  • Venus Shahabi Raberi Department of Cardiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Samira Abdollahi Moghadam Gynecologist and Obstetrician, Women's Reproductive Health Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  • Ensieh Sharafi Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  • Maryam Poudineh School of Medicine, Mashhad Azad University, Mashhad, Iran
  • Behnaz Barghgir School of Medicine, Shahrud University, Shahrud, Iran
  • Maryam Molaee Eshgh Abad School of Medicine, Shahrud University, Shahrud, Iran
  • Morteza Jafarinia Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Hossein Kargar Jahromi Research Center for Non-Communicable Disease, Jahrom University of Medical Sciences, Jahrom, Iran; Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran
Keywords: Mesenchymal Stem Cells, Tumor, Cancer, Tumor Microenvironment, Mesenchymal Stromal Cells


Mesenchymal stromal/stem cells (MSCs) are a source of stem cells that can be easily harvested and differentiated into numerous cells. Over the past few decades, these cells have been introduced as promising therapeutic candidates for different diseases. Different studies have shown the role of these cells in regenerative medicine. Tumor growth is correlated with the interactions between MSCs and tumor cells in the tumor microenvironment. The precise key role played by MSCs in the progression of tumors is under question, and the effect of MSCs on the tumor is controversial it might involve the development of tumor initiation or prevent the spread of already existing ones. In this study, we reviewed the role of MSCs in the tumor microenvironment and their influence on promoting or inhibiting tumor progression.


Jafarinia M, Alsahebfosoul F, Salehi H, Eskandari N, Ganjalikhani-Hakemi M. Mesenchymal stem cell-derived extracellular vesicles: a novel cell-free therapy. Immunol Invest. 2020;49(7):758-80.


Jafarinia M, Amoon M, Javid A, Vakili S, Sadeghi E, Azadi D, et al. Male microchimerism in peripheral blood from women with multiple sclerosis in Isfahan Province. Int J Immunogenet. 2020;47(2):175-9.


Fazal-ur-Rehman M, Qayyum I. Biomedical scope of gold nanoparticles in medical sciences; an advancement in cancer therapy. J Med Chem Sci. 2020;3(4):399-407.

Hamidipour N, Fazeli M, Hedayati M, Dehghani M, Gerami R. PI3K/Akt/mTOR and CDK4 combined inhibition enhanced apoptosis of thyroid cancer cell lines. Int J Adv Biol Biomed Res. 2020;8(2):214-24.

Gholami A, Mehrabi F. Cancer and nanotechnology: A mini review. AANBT. 2022;3(1):1-6.

Yousefi K. Graphene based nanostructure interaction with human liver cancer cells. AANBT. 2021;2(4):60-71.

Kalashgrani MY, Javanmardi N. Multifunctional Gold nanoparticle: As novel agents for cancer treatment. AANBT. 2022:43-8.

Javanmardi N, Javidi Z, Mazraedoost S, Omidi Y, Hosseini AH, Mokhberi M. The Advances in nanostructures vaccine, new approaches to improve for anticancer and immune system efficiency. AANBT. 2021;2(4):102-11.

Dvorak HF. Tumors: wounds that do not heal. N Engl J Med. 1986;315(26):1650-9.


Chang AI, Schwertschkow AH, Nolta JA, Wu J. Involvement of mesenchymal stem cells in cancer progression and metastases. Curr Cancer Drug Targets. 2015;15(2):88-98.


Shadmanesh A, Nazari H, Shirazi A, Ahmadi E, Shams-Esfandabadi N. An inexpensive and simple method for isolation mesenchymal stem cell of human amnion membrane. Int J Adv Biol Biomed Res. 2021;9(1):119-27.

Reagan MR, Kaplan DL. Concise review: mesenchymal stem cell tumor-homing: detection methods in disease model systems. Stem Cells. 2011;29(6):920-7.

PMid:21557390 PMCid:PMC4581846

Chen X, Armstrong MA, Li G. Mesenchymal stem cells in immunoregulation. Immunol Cell Biol. 2006;84(5):413-21.


Kim SM, Lim JY, Park SI, Jeong CH, Oh JH, Jeong M, et al. Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma. Cancer Res. 2008;68(23):9614-23.


Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. The Lancet. 2008;371(9624):1579-86.


Ringe J, Strassburg S, Neumann K, Endres M, Notter M, Burmester GR, et al. Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. J Cell Biochem. 2007;101(1):135-46.


Song C, Li G. CXCR4 and matrix metalloproteinase-2 are involved in mesenchymal stromal cell homing and engraftment to tumors. Cytotherapy. 2011;13(5):549-61.


Schlosser S, Dennler C, Schweizer R, Eberli D, Stein JV, Enzmann V, et al. Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin. Microvasc Res. 2012;83(3):267-75.


Shome S, Dasgupta PS, Basu S. Dopamine regulates mobilization of mesenchymal stem cells during wound angiogenesis. PLoS One. 2012;7(2):e31682.

PMid:22355389 PMCid:PMC3280323

Albarenque SM, Zwacka RM, Mohr A. Both human and mouse mesenchymal stem cells promote breast cancer metastasis. Stem Cell Res. 2011;7(2):163-71.


Shinagawa K, Kitadai Y, Tanaka M, Sumida T, Kodama M, Higashi Y, et al. Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer. 2010;127(10):2323-33.


Ediz S, Cancan M, Alaeiyan M, Farahani MR. Ve-degree and Ev-degree topological analysis of some anticancer drugs. Eurasian Chem Commun. 2020;2(8):834-40.

Duda DG, Duyverman AM, Kohno M, Snuderl M, Steller EJ, Fukumura D, et al. Malignant cells facilitate lung metastasis by bringing their own soil. Proc Natl Acad Sci. 2010;107(50):21677-82.

PMid:21098274 PMCid:PMC3003109

Chaturvedi P, Gilkes DM, Wong CCL, Luo W, Zhang H, Wei H, et al. Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Investig. 2012;123(1):189-205.

PMid:23318994 PMCid:PMC3533298

Martin F, Dwyer RM, Kelly J, Khan S, Murphy J, Curran C, et al. Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat. 2010;124(2):317-26.


Xue Z, Wu X, Chen X, Liu Y, Wang X, Wu K, et al. Mesenchymal stem cells promote epithelial to mesenchymal transition and metastasis in gastric cancer though paracrine cues and close physical contact. J Cell Biochem. 2015;116(4):618-27.


Jing Y, Han Z, Liu Y, Sun K, Zhang S, Jiang G, et al. Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition. PLoS One. 2012;7(8):e43272.

PMid:22952657 PMCid:PMC3429457

El-Haibi CP, Bell GW, Zhang J, Collmann AY, Wood D, Scherber CM, et al. Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. Proc Natl Acad Sci. 2012;109(43):17460-5.

PMid:23033492 PMCid:PMC3491529

Xu Q, Wang L, Li H, Han Q, Li J, Qu X, et al. Mesenchymal stem cells play a potential role in regulating the establishment and maintenance of epithelial-mesenchymal transition in MCF7 human breast cancer cells by paracrine and induced autocrine TGF-β. Int J Oncol. 2012;41(3):959-68.


Kabashima‐Niibe A, Higuchi H, Takaishi H, Masugi Y, Matsuzaki Y, Mabuchi Y, et al. Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells. Cancer Sci. 2013;104(2):157-64.

PMid:23121112 PMCid:PMC7657182

Hall B, Andreeff M, Marini F. The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles. Handb Exp Pharmacol. 2007;(180):263-83.


Casiraghi F, Perico N, Remuzzi G. Mesenchymal stromal cells to promote solid organ transplantation tolerance. Curr Opin Organ Transplant. 2013;18(1):51-8.


Reinders ME, Bank JR, Dreyer GJ, Roelofs H, Heidt S, Roelen DL, et al. Autologous bone marrow derived mesenchymal stromal cell therapy in combination with everolimus to preserve renal structure and function in renal transplant recipients. J Transl Med. 2014;12(1):1-12.

PMid:25491391 PMCid:PMC4273432

Glenn JD, Whartenby KA. Mesenchymal stem cells: emerging mechanisms of immunomodulation and therapy. World J Stem Cells. 2014;6(5):526.

PMid:25426250 PMCid:PMC4178253

Groh ME, Maitra B, Szekely E, Koç ON. Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol. 2005;33(8):928-34.


Batten P, Sarathchandra P, Antoniw JW, Tay SS, Lowdell MW, Taylor PM, et al. Human mesenchymal stem cells induce T cell anergy and downregulate T cell allo-responses via the TH2 pathway: relevance to tissue engineering human heart valves. Tissue Eng. 2006;12(8):2263-73.


Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, et al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. 2007;109(1):228-34.


Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815-22.


Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2, 3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103(12):4619-21.


Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014;32(3):252-60.

PMid:24561556 PMCid:PMC4320647

Owens SD, Kol A, Walker NJ, Borjesson DL. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses. Stem Cells Int. 2016;2016:5830103.

PMid:27648075 PMCid:PMC5018342

Lee M, Jeong SY, Ha J, Kim M, Jin HJ, Kwon S-J, et al. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo. Biochem Biophys Res Commun. 2014;446(4):983-9.


Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P. Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol. 2010;184(10):5885-94.


Han Z, Tian Z, Lv G, Zhang L, Jiang G, Sun K, et al. Immunosuppressive effect of bone marrow‐derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells. J Cell Mol Med. 2011;15(11):2343-52.

PMid:21091630 PMCid:PMC3822946

Cheng J, Li L, Liu Y, Wang Z, Zhu X, Bai X. Interleukin-1α induces immunosuppression by mesenchymal stem cells promoting the growth of prostate cancer cells. Mol Med Report. 2012;6(5):955-60.


Beckermann B, Kallifatidis G, Groth A, Frommhold D, Apel A, Mattern J, et al. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer. 2008;99(4):622-31.

PMid:18665180 PMCid:PMC2527820

Suzuki K, Sun R, Origuchi M, Kanehira M, Takahata T, Itoh J, et al. Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Mol Med. 2011;17(7):579-87.

PMid:21424106 PMCid:PMC3146617

Liu Y, Han ZP, Zhang SS, Jing YY, Bu XX, Wang CY, et al. Effects of inflammatory factors on mesenchymal stem cells and their role in the promotion of tumor angiogenesis in colon cancer. J Biol Chem. 2011;286(28):25007-15.

PMid:21592963 PMCid:PMC3137074

Billadeau DD, Nolz JC, Gomez TS. Regulation of T-cell activation by the cytoskeleton. Nat Rev Immunol. 2007;7(2):131-43.


Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Migrating cancer stem cells-an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005;5(9):744-9.


Cho ES, Kang HE, Kim NH, Yook JI. Therapeutic implications of cancer epithelial-mesenchymal transition (EMT). Arch Pharm Res. 2019;42(1):14-24.


Klopp AH, Lacerda L, Gupta A, Debeb BG, Solley T, Li L, et al. Mesenchymal stem cells promote mammosphere formation and decrease E-cadherin in normal and malignant breast cells. PLoS One. 2010;5(8):e12180.

PMid:20808935 PMCid:PMC2922340

Rhodes LV, Antoon JW, Muir SE, Elliott S, Beckman BS, Burow ME. Effects of human mesenchymal stem cells on ER-positive human breast carcinoma cells mediated through ER-SDF-1/CXCR4 crosstalk. Mol Cancer. 2010;9(1):1-15.

PMid:21087507 PMCid:PMC2998478

Halpern JL, Kilbarger A, Lynch CC. Mesenchymal stem cells promote mammary cancer cell migration in vitro via the CXCR2 receptor. Cancer Lett. 2011;308(1):91-9.

PMid:21601983 PMCid:PMC3311035

Ye H, Cheng J, Tang Y, Liu Z, Xu C, Liu Y, et al. Human bone marrow-derived mesenchymal stem cells produced TGFbeta contributes to progression and metastasis of prostate cancer. Cancer Invest. 2012;30(7):513-8.


Liu S, Ginestier C, Ou SJ, Clouthier SG, Patel SH, Monville F, et al. Breast Cancer Stem Cells Are Regulated by Mesenchymal Stem Cells through Cytokine NetworksMSCs Regulate Breast Cancer Stem Cells. Cancer Res. 2011;71(2):614-24.

PMid:21224357 PMCid:PMC3100554

McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S, et al. Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Investig. 2011;121(8):3206-19.

PMid:21737876 PMCid:PMC3148732

Nishimura K, Semba S, Aoyagi K, Sasaki H, Yokozaki H. Mesenchymal stem cells provide an advantageous tumor microenvironment for the restoration of cancer stem cells. Pathobiology. 2012;79(6):290-306.


Hsu HS, Lin JH, Hsu TW, Su K, Wang CW, Yang KY, et al. Mesenchymal stem cells enhance lung cancer initiation through activation of IL-6/JAK2/STAT3 pathway. Lung Cancer. 2012;75(2):167-77.


Li H, Reinhardt F, Herschman H. A Weinberg, R. Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling. Cancer Discov. 2012;2:840-55.

PMid:22763855 PMCid:PMC3833451

Ohlsson LB, Varas L, Kjellman C, Edvardsen K, Lindvall M. Mesenchymal progenitor cell-mediated inhibition of tumor growth in vivo and in vitro in gelatin matrix. Exp Mol Pathol. 2003;75(3):248-55.


Khakoo AY, Pati S, Anderson SA, Reid W, Elshal MF, Rovira II, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma. J Exp Med. 2006;203(5):1235-47.

PMid:16636132 PMCid:PMC2121206

Qiao L, Xu ZL, Zhao TJ, Ye LH, Zhang XD. Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling. Cancer Lett. 2008;269(1):67-77.


Lu YR, Yuan Y, Wang XJ, Wei LL, Chen YN, Cong C, et al. The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo. Cancer Biol Ther. 2008;7(2):245-51.


Otsu K, Das S, Houser SD, Quadri SK, Bhattacharya S, Bhattacharya J. Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells. Blood. 2009;113(18):4197-205.

PMid:19036701 PMCid:PMC2676081

Gu H, Yan C, Wan H, Wu L, Liu J, Zhu Z, et al. Mesenchymal stem cell-derived exosomes block malignant behaviors of hepatocellular carcinoma stem cells through a lncRNA C5orf66-AS1/microRNA-127-3p/DUSP1/ERK axis. Hum Cell. 2021;34(6):1812-29.


Loebinger M, Sage E, Davies D, Janes S. TRAIL-expressing mesenchymal stem cells kill the putative cancer stem cell population. Br J Cancer. 2010;103(11):1692-7.

PMid:21063402 PMCid:PMC2994223

Sadhukha T, O'Brien TD, Prabha S. Nano-engineered mesenchymal stem cells as targeted therapeutic carriers. J Control Release. 2014;196:243-51.


Spaw M, Anant S, Thomas SM. Stromal contributions to the carcinogenic process. Mol Carcinog. 2017;56(4):1199-213.

PMid:27787930 PMCid:PMC5354948

Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One. 2010;5(4):e10088.

PMid:20436665 PMCid:PMC2859930

Waterman RS, Henkle SL, Betancourt AM. Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis. PLoS One. 2012:7(9):e45590.

PMid:23029122 PMCid:PMC3447765

Rivera-Cruz CM, Shearer JJ, Figueiredo Neto M, Figueiredo ML. The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche. Stem Cells Int. 2017;2017:4015039.

PMid:29181035 PMCid:PMC5664329

Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Robey PG, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15(1):42-9.

PMid:19098906 PMCid:PMC2706487

Bai L, Lennon DP, Eaton V, Maier K, Caplan AI, Miller SD, et al. Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009;57(11):1192-203.

PMid:19191336 PMCid:PMC2706928

Niu J, Yue W, Le-Le Z, Bin L, Hu X. Mesenchymal stem cells inhibit T cell activation by releasing TGF-β1 from TGF-β1/GARP complex. Oncotarget. 2017;8(59):99784.

PMid:29245940 PMCid:PMC5725131

Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor ζ-chain and induce a regulatory phenotype in naive T Cells. J Immunol. 2006;176(11):6752-61.


Lee HJ, Ko JH, Jeong HJ, Ko AY, Kim MK, Wee WR, et al. Mesenchymal stem/stromal cells protect against autoimmunity via CCL2-dependent recruitment of myeloid-derived suppressor cells. J Immunol. 2015;194(8):3634-45.


Asari S, Itakura S, Ferreri K, Liu CP, Kuroda Y, Kandeel F, et al. Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol. 2009;37(5):604-15.

PMid:19375651 PMCid:PMC2747661

Ungerer C, Quade-Lyssy P, Radeke HH, Henschler R, Königs C, Köhl U, et al. Galectin-9 is a suppressor of T and B cells and predicts the immune modulatory potential of mesenchymal stromal cell preparations. Stem Cells Dev. 2014;23(7):755-66.

PMid:24083426 PMCid:PMC3967371

Galland S, Vuille J, Martin P, Letovanec I, Caignard A, Fregni G, et al. Tumor-derived mesenchymal stem cells use distinct mechanisms to block the activity of natural killer cell subsets. Cell Rep. 2017;20(12):2891-905.


Spaggiari GM, Abdelrazik H, Becchetti F, Moretta L. MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood. 2009;113(26):6576-83.


Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105(10):4120-6.


Chen B, Ni Y, Liu J, Zhang Y, Yan F. Bone Marrow-Derived Mesenchymal Stem Cells Exert Diverse Effects on Different Macrophage Subsets. Stem Cells Int. 2018;2018:8348121.

PMid:30140291 PMCid:PMC6081573

Vasandan AB, Jahnavi S, Shashank C, Prasad P, Kumar A, Prasanna SJ. Human Mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE2-dependent mechanism. Sci Rep. 2016;6(1):1-17.

PMid:27910911 PMCid:PMC5133610

Hu X, Zhou Y, Dong K, Sun Z, Zhao D, Wang W, et al. Programming of the development of tumor-promoting neutrophils by mesenchymal stromal cells. Cell Physiol Biochem. 2014;33(6):1802-14.


Zhu Q, Zhang X, Zhang L, Li W, Wu H, Yuan X, et al. The IL-6-STAT3 axis mediates a reciprocal crosstalk between cancer-derived mesenchymal stem cells and neutrophils to synergistically prompt gastric cancer progression. Cell Death Dis. 2014;5(6):e1295-e.

PMid:24946088 PMCid:PMC4611735

Zhang T, Lee YW, Rui YF, Cheng TY, Jiang XH, Li G. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res Ther. 2013;4(3):1-15.

PMid:23763837 PMCid:PMC3707041

Li GC, Zhang HW, Zhao QC, Sun L, Yang JJ, Hong L, et al. Mesenchymal stem cells promote tumor angiogenesis via the action of transforming growth factor β1. Oncol Lett. 2016;11(2):1089-94.

PMid:26893697 PMCid:PMC4733964

Yuan Z, Bian Y, Ma X, Tang Z, Chen N, Shen M. LncRNA H19 knockdown in human amniotic mesenchymal stem cells suppresses angiogenesis by associating with EZH2 and activating vasohibin-1. Stem Cells Dev. 2019;28(12):781-90.


Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438(7069):820-7.

PMid:16341007 PMCid:PMC2945882

Bergfeld SA, DeClerck YA. Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev. 2010;29(2):249-61.


Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557-63.


Hung SC, Pochampally RR, Chen SC, Hsu SC, Prockop DJ. Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells. 2007;25(9):2363-70.


Dias S, Choy M, Alitalo K, Rafii S. Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. Blood. 2002;99(6):2179-84.


König A, Menzel T, Lynen S, Wrazel L, Rosen A, Al-Katib A, et al. Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis. Leukemia. 1997;11(2):258-65.


Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps TJ. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000;96(8):2655-63.


Efimenko A, Starostina E, Kalinina N, Stolzing A. Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med. 2011;9(1):1-13.

PMid:21244679 PMCid:PMC3033332

Naderi EH, Skah S, Ugland H, Myklebost O, Sandnes DL, Torgersen ML, et al. Bone marrow stroma-derived PGE2 protects BCP-ALL cells from DNA damage-induced p53 accumulation and cell death. Mol Cancer. 2015;14(1):1-12.

PMid:25623255 PMCid:PMC4323193

Bonuccelli G, Avnet S, Grisendi G, Salerno M, Granchi D, Dominici M, et al. Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells. Oncotarget. 2014;5(17):7575.

PMid:25277190 PMCid:PMC4202145

Miyazaki Y, Oda T, Mori N, Kida YS. Adipose-derived mesenchymal stem cells differentiate into pancreatic cancer-associated fibroblasts in vitro. FEBS Open Bio. 2020;10(11):2268-81.

PMid:32931156 PMCid:PMC7609785

Liu B, Ma X, Liu Q, Xiao Y, Pan S, Jia L. Retraction Note: Aberrant mannosylation profile and FTX/miR-342/ALG3-axis contribute to development of drug resistance in acute myeloid leukemia. Cell Death Dis. 2020;11(2):122.

PMid:32051397 PMCid:PMC7015917

He W, Liang B, Wang C, Li S, Zhao Y, Huang Q, et al. MSC-regulated lncRNA MACC1-AS1 promotes stemness and chemoresistance through fatty acid oxidation in gastric cancer. Oncogene. 2019;38(23):4637-54.

PMid:30742067 PMCid:PMC6756048

Tu Z, Schmöllerl J, Cuiffo BG, Karnoub AE. Microenvironmental regulation of long noncoding RNA LINC01133 promotes cancer stem cell-like phenotypic traits in triple-negative breast cancers. Stem Cells. 2019;37(10):1281-92.


How to Cite
Shahabi Raberi , V., Abdollahi Moghadam, S., Sharafi , E., Poudineh, M., Barghgir, B., Molaee Eshgh Abad , M., Jafarinia , M., & Kargar Jahromi, H. (2022). Mesenchymal Stromal/Stem Cells in the Tumor Microenvironment and Their Role in Tumor Progression. Galen Medical Journal, 11, e2637.
Review Article