Mesenchymal stem cells in progression and treatment of cancers

doi:10.1007/s11515-014-1306-2

Front. Biol.

2014, Vol. 9

Issue (3) : 186-194 https://doi.org/10.1007/s11515-014-1306-2

REVIEW

Mesenchymal stem cells in progression and treatment of cancers

Qingguo ZHAO,Fei LIU(

)

Institute for Regenerative Medicine at Scott & White, MCMD, Texas A&M Health Science Center, Temple, TX 76502, USA

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Abstract

Mesenchymal stem or stromal cells (MSCs) from bone marrow or local tissues are recruited to stroma of almost all types of cancers during initiation and/or progression of cancer. The recruited MSCs and their derivative cancer-associated fibroblasts interact with cancer cells to promote stemness, invasion and metastasis of cancer cells. Targeting these cancer-recruited MSCs and/or the interaction between MSCs and cancer cells are promising strategies to improve cancer therapy. On the other hand, the unique tumor-homing capacity of MSCs makes them a promising vehicle to deliver various anti-cancer agents. This review summarized the recent advancement of our understanding on the interaction between MSCs and cancer cells, as well as the potential of MSCs for cancer therapy.

Keywords mesenchymal stem or stromal cells cancer cancer-associated fibroblasts gene therapy cell therapy

Corresponding Author(s): Fei LIU

Issue Date: 24 June 2014

Cite this article:

Qingguo ZHAO,Fei LIU. Mesenchymal stem cells in progression and treatment of cancers[J]. Front. Biol., 2014, 9(3): 186-194.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-014-1306-2
https://academic.hep.com.cn/fib/EN/Y2014/V9/I3/186

Fig.1 Recuritment of MSCs to primary or metastatic cancer. Primary cancer produces various factors to moblize MSCs in bone marrow (1A) or local tissues and to creat premetastatic niche in remote organs such as lungs (1B). Moblized MSCs migrate to primary cancer (2A) or the premetastatic niche (2B), then interact with cancer cells and promote metastasis of cancer (3).

Fig.2 Interactions between cancer cells, recruited MSCs and CAFs. Cancer cells produce various factors to stimulate the production of pro-tumor factors and CAF differentiation of recurited MSCs. The pro-tumor factors produced by MSCs and CAFs promote growth and EMT of cancer cells and consequent invasion, metastasis and CSC expansion. These MSCs and CAFs also promote angiogenesis and protect cancer cells from immune destruction.

Tab.1 Agents delivered by MSCs to treat cancer.

1	BolontradeM F, SgangaL, PiaggioE, VialeD L, SorrentinoM A, RobinsonA, SevleverG, GarcíaM G, MazzoliniG, PodhajcerO L (2012). A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus. Stem Cells Dev, 21(14): 2689–2702 doi: 10.1089/scd.2011.0643 pmid: 22462538
2	BrunoS, CollinoF, DeregibusM C, GrangeC, TettaC, CamussiG (2013). Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth. Stem Cells Dev, 22(5): 758–771 doi: 10.1089/scd.2012.0304 pmid: 23034046
3	CarreroR, CerradaI, LledóE, DopazoJ, García-GarcíaF, RubioM P, TriguerosC, DorronsoroA, Ruiz-SauriA, MonteroJ A, SepúlvedaP (2012). IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB. Stem Cell Rev, 8(3): 905–916 doi: 10.1007/s12015-012-9364-9 pmid: 22467443
4	CastletonA, DeyA, BeatonB, PatelB, AucherA, DavisD M, FieldingA K (2014). Human mesenchymal stromal cells deliver systemic oncolytic measles virus to treat acute lymphoblastic leukemia in the presence of humoral immunity. Blood, 123(9): 1327–1335 doi: 10.1182/blood-2013-09-528851 pmid: 24345754
5	CavarrettaI T, AltanerovaV, MatuskovaM, KucerovaL, CuligZ, AltanerC (2010). Adipose tissue-derived mesenchymal stem cells expressing prodrug-converting enzyme inhibit human prostate tumor growth. Mol Ther, 18(1): 223–231 doi: 10.1038/mt.2009.237 pmid: 19844197
6	ChaturvediP, GilkesD M, WongC C, LuoW, ZhangH, WeiH, TakanoN, SchitoL, LevchenkoA, SemenzaG L, and the Kshitiz (2013). Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest, 123(1): 189–205 pmid: 23318994
7	ChenM Y, LieP C, LiZ L, WeiX (2009). Endothelial differentiation of Wharton’s jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells. Exp Hematol, 37(5): 629–640 doi: 10.1016/j.exphem.2009.02.003 pmid: 19375653
8	De BoeckA, PauwelsP, HensenK, RummensJ L, WestbroekW, HendrixA, MaynardD, DenysH, LambeinK, BraemsG, GespachC, BrackeM, De WeverO (2013). Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling. Gut, 62(4): 550–560 doi: 10.1136/gutjnl-2011-301393 pmid: 22535374
9	de PeppoG M, Marcos-CamposI, KahlerD J, AlsalmanD, ShangL, Vunjak-NovakovicG, MaroltD (2013). Engineering bone tissue substitutes from human induced pluripotent stem cells. Proc Natl Acad Sci USA, 110(21): 8680–8685 doi: 10.1073/pnas.1301190110 pmid: 23653480
10	Di StasiA, TeyS K, DottiG, FujitaY, Kennedy-NasserA, MartinezC, StraathofK, LiuE, DurettA G, GrilleyB, LiuH, CruzC R, SavoldoB, GeeA P, SchindlerJ, KranceR A, HeslopH E, SpencerD M, RooneyC M, BrennerM K (2011). Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med, 365(18): 1673–1683 doi: 10.1056/NEJMoa1106152 pmid: 22047558
11	DuchiS, SotgiuG, LucarelliE, BallestriM, DozzaB, SantiS, GuerriniA, DambruosoP, GianniniS, DonatiD, FerroniC, VarchiG (2013). Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: effective photoinduced in vitro killing of osteosarcoma. J Control Release, 168(2): 225–237 doi: 10.1016/j.jconrel.2013.03.012 pmid: 23524189
12	DvorakH F (1986). Tumors: wounds that do not heal.Similarities between tumor stroma generation and wound healing. N Engl J Med, 315(26): 1650–1659 doi: 10.1056/NEJM198612253152606 pmid: 3537791
13	El-HaibiC P, BellG W, ZhangJ, CollmannA Y, WoodD, ScherberC M, CsizmadiaE, MarianiO, ZhuC, CampagneA, TonerM, BhatiaS N, IrimiaD, Vincent-SalomonA, KarnoubA E (2012). Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. Proc Natl Acad Sci USA, 109(43): 17460–17465 doi: 10.1073/pnas.1206653109 pmid: 23033492
14	ErlerJ T, BennewithK L, CoxT R, LangG, BirdD, KoongA, LeQ T, GiacciaA J (2009). Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell, 15(1): 35–44 doi: 10.1016/j.ccr.2008.11.012 pmid: 19111879
15	García-CastroJ, AlemanyR, CascallóM, Martínez-QuintanillaJ, ArrieroM M, LassalettaA, MaderoL, RamírezM (2010). Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study. Cancer Gene Ther, 17(7): 476–483 doi: 10.1038/cgt.2010.4 pmid: 20168350
16	GoldenbergD M, GoldD V, LooM, LiuD, ChangC H, JaffeE S (2013). Horizontal transmission of malignancy: in-vivo fusion of human lymphomas with hamster stroma produces tumors retaining human genes and lymphoid pathology. PLoS ONE, 8(2): e55324 doi: 10.1371/journal.pone.0055324 pmid: 23405135
17	GrisendiG, BussolariR, CafarelliL, PetakI, RasiniV, VeronesiE, De SantisG, SpanoC, TagliazzucchiM, Barti-JuhaszH, ScarabelliL, BambiF, FrassoldatiA, RossiG, CasaliC, MorandiU, HorwitzE M, PaolucciP, ConteP, DominiciM (2010). Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res, 70(9): 3718–3729 doi: 10.1158/0008-5472.CAN-09-1865 pmid: 20388793
18	HoI A, TohH C, NgW H, TeoY L, GuoC M, HuiK M, LamP Y (2013). Human bone marrow-derived mesenchymal stem cells suppress human glioma growth through inhibition of angiogenesis. Stem Cells, 31(1): 146–155 doi: 10.1002/stem.1247 pmid: 23034897
19	HongH S, LeeJ, LeeE, KwonY S, LeeE, AhnW, JiangM H, KimJ C, SonY (2009). A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells. Nat Med, 15(4): 425–435 doi: 10.1038/nm.1909 pmid: 19270709
20	HoughtonJ, StoicovC, NomuraS, RogersA B, CarlsonJ, LiH, CaiX, FoxJ G, GoldenringJ R, WangT C (2004). Gastric cancer originating from bone marrow-derived cells. Science, 306(5701): 1568–1571 doi: 10.1126/science.1099513 pmid: 15567866
21	IpJ E, WuY, HuangJ, ZhangL, PrattR E, DzauV J (2007). Mesenchymal stem cells use integrin beta1 not CXC chemokine receptor 4 for myocardial migration and engraftment. Mol Biol Cell, 18(8): 2873–2882 doi: 10.1091/mbc.E07-02-0166 pmid: 17507648
22	JacobsenB M, HarrellJ C, JedlickaP, BorgesV F, Varella-GarciaM, HorwitzK B (2006). Spontaneous fusion with, and transformation of mouse stroma by, malignant human breast cancer epithelium. Cancer Res, 66(16): 8274–8279 doi: 10.1158/0008-5472.CAN-06-1456 pmid: 16912208
23	JohannP D, VaeglerM, GiesekeF, MangP, Armeanu-EbingerS, KlubaT, HandgretingerR, MüllerI (2010). Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity. BMC Cancer, 10(1): 501 doi: 10.1186/1471-2407-10-501 pmid: 20858262
24	JungY, KimJ K, ShiozawaY, WangJ, MishraA, JosephJ, BerryJ E, McGeeS, LeeE, SunH, WangJ, JinT, ZhangH, DaiJ, KrebsbachP H, KellerE T, PientaK J, TaichmanR S (2013). Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis. Nat Commun, 4: 1795 doi: 10.1038/ncomms2766 pmid: 23653207
25	KarnoubA E, DashA B, VoA P, SullivanA, BrooksM W, BellG W, RichardsonA L, PolyakK, TuboR, WeinbergR A (2007). Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 449(7162): 557–563 doi: 10.1038/nature06188 pmid: 17914389
26	KhakooA Y, PatiS, AndersonS A, ReidW, ElshalM F, RoviraI I, NguyenA T, MalideD, CombsC A, HallG, ZhangJ, RaffeldM, RogersT B, Stetler-StevensonW, FrankJ A, ReitzM, FinkelT (2006). Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med, 203(5): 1235–1247 doi: 10.1084/jem.20051921 pmid: 16636132
27	KiddS, CaldwellL, DietrichM, SamudioI, SpaethE L, WatsonK, ShiY, AbbruzzeseJ, KonoplevaM, AndreeffM, MariniF C (2010). Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment. Cytotherapy, 12(5): 615–625 doi: 10.3109/14653241003631815 pmid: 20230221
28	KimS W, KimS J, ParkS H, YangH G, KangM C, ChoiY W, KimS M, JeunS S, SungY C (2013). Complete regression of metastatic renal cell carcinoma by multiple injections of engineered mesenchymal stem cells expressing dodecameric TRAIL and HSV-TK. Clin Cancer Res, 19(2): 415–427 doi: 10.1158/1078-0432.CCR-12-1568 pmid: 23204131
29	KinnairdT, StabileE, BurnettM S, LeeC W, BarrS, FuchsS, EpsteinS E (2004). Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res, 94(5): 678–685 doi: 10.1161/01.RES.0000118601.37875.AC pmid: 14739163
30	KitadaiY, SasakiT, KuwaiT, NakamuraT, BucanaC D, HamiltonS R, FidlerI J (2006). Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potential. Int J Cancer, 119(11): 2567–2574 doi: 10.1002/ijc.22229 pmid: 16988946
31	Kolluri,K.K., Laurent,G.J., and Janes,S.M. (2013). Mesenchymal stem cells as vectors for lung cancer therapy. Respiration; international review of thoracic diseases85, 443–451.
32	KomlevV S, MastrogiacomoM, PeyrinF, CanceddaR, RustichelliF (2009). X-ray synchrotron radiation pseudo-holotomography as a new imaging technique to investigate angio- and microvasculogenesis with no usage of contrast agents. Tissue Eng Part C Methods, 15(3): 425–430 doi: 10.1089/ten.tec.2008.0428 pmid: 19231984
33	KramanM, BambroughP J, ArnoldJ N, RobertsE W, MagieraL, JonesJ O, GopinathanA, TuvesonD A, FearonD T (2010). Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science, 330(6005): 827–830 doi: 10.1126/science.1195300 pmid: 21051638
34	KrausgrillB, VantlerM, BurstV, RathsM, HalbachM, FrankK, SchynkowskiS, SchenkK, HeschelerJ, RosenkranzS, Müller-EhmsenJ (2009). Influence of cell treatment with PDGF-BB and reperfusion on cardiac persistence of mononuclear and mesenchymal bone marrow cells after transplantation into acute myocardial infarction in rats. Cell Transplant, 18(8): 847–853 doi: 10.3727/096368909X471134 pmid: 19520046
35	KucerovaL, AltanerovaV, MatuskovaM, TyciakovaS, AltanerC (2007). Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy. Cancer Res, 67(13): 6304–6313 doi: 10.1158/0008-5472.CAN-06-4024 pmid: 17616689
36	KucerovaL, MatuskovaM, PastorakovaA, TyciakovaS, JakubikovaJ, BohovicR, AltanerovaV, AltanerC (2008). Cytosine deaminase expressing human mesenchymal stem cells mediated tumour regression in melanoma bearing mice. J Gene Med, 10(10): 1071–1082 doi: 10.1002/jgm.1239 pmid: 18671316
37	LarsonB L, YlostaloJ, LeeR H, GregoryC, ProckopD J (2010). Sox11 is expressed in early progenitor human multipotent stromal cells and decreases with extensive expansion of the cells. Tissue Eng Part A, 16(11): 3385–3394 doi: 10.1089/ten.tea.2010.0085 pmid: 20626275
38	LazovaR, LabergeG S, DuvallE, SpoelstraN, KlumpV, SznolM, CooperD, SpritzR A, ChangJ T, PawelekJ M (2013). A melanoma brain metastasis with a donor-patient hybrid genome following bone marrow transplantation: first evidence for fusion in human cancer. PLoS ONE, 8(6): e66731 doi: 10.1371/journal.pone.0066731 pmid: 23840523
39	LeeR H, PulinA A, SeoM J, KotaD J, YlostaloJ, LarsonB L, Semprun-PrietoL, DelafontaineP, ProckopD J (2009a). Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell, 5(1): 54–63 doi: 10.1016/j.stem.2009.05.003 pmid: 19570514
40	LeeR H, SeoM J, PulinA A, GregoryC A, YlostaloJ, ProckopD J (2009b). The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood, 113(4): 816–826 doi: 10.1182/blood-2007-12-128702 pmid: 18818395
41	LeeR H, YoonN, ReneauJ C, ProckopD J (2012). Preactivation of human MSCs with TNF-α enhances tumor-suppressive activity. Cell Stem Cell, 11(6): 825–835 doi: 10.1016/j.stem.2012.10.001 pmid: 23142520
42	LesleyJ, GálI, MahoneyD J, CordellM R, RuggM S, HymanR, DayA J, MikeczK (2004). TSG-6 modulates the interaction between hyaluronan and cell surface CD44. J Biol Chem, 279(24): 25745–25754 doi: 10.1074/jbc.M313319200 pmid: 15060082
43	LiH J, ReinhardtF, HerschmanH R, WeinbergR A (2012). Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling. Cancer Discov, 2(9): 840–855 doi: 10.1158/2159-8290.CD-12-0101 pmid: 22763855
44	LinR, MaH, DingZ, ShiW, QianW, SongJ, HouX (2013). Bone marrow-derived mesenchymal stem cells favor the immunosuppressive T cells skewing in a Helicobacter pylori model of gastric cancer. Stem Cells Dev, 22(21): 2836–2848 doi: 10.1089/scd.2013.0166 pmid: 23777268
45	LiuS, GinestierC, OuS J, ClouthierS G, PatelS H, MonvilleF, KorkayaH, HeathA, DutcherJ, KleerC G, JungY, DontuG, TaichmanR, WichaM S (2011a). Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res, 71(2): 614–624 doi: 10.1158/0008-5472.CAN-10-0538 pmid: 21224357
46	LiuY, HanZ P, ZhangS S, JingY Y, BuX X, WangC Y, SunK, JiangG C, ZhaoX, LiR, GaoL, ZhaoQ D, WuM C, WeiL X (2011b). Effects of inflammatory factors on mesenchymal stem cells and their role in the promotion of tumor angiogenesis in colon cancer. J Biol Chem, 286(28): 25007–25015 doi: 10.1074/jbc.M110.213108 pmid: 21592963
47	LoebingerM R, EddaoudiA, DaviesD, JanesS M (2009). Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res, 69(10): 4134–4142 doi: 10.1158/0008-5472.CAN-08-4698 pmid: 19435900
48	LoebingerM R, JanesS M (2010). Stem cells as vectors for antitumour therapy. Thorax, 65(4): 362–369 doi: 10.1136/thx.2009.128025 pmid: 20388765
49	LuY R, YuanY, WangX J, WeiL L, ChenY N, CongC, LiS F, LongD, TanW D, MaoY Q, ZhangJ, LiY P, ChengJ Q (2008). The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo. Cancer Biol Ther, 7(2): 245–251 doi: 10.4161/cbt.7.2.5296 pmid: 18059192
50	MaderE K, MaeyamaY, LinY, ButlerG W, RussellH M, GalanisE, RussellS J, DietzA B, PengK W (2009). Mesenchymal stem cell carriers protect oncolytic measles viruses from antibody neutralization in an orthotopic ovarian cancer therapy model. Clin Cancer Res, 15(23): 7246–7255 doi: 10.1158/1078-0432.CCR-09-1292 pmid: 19934299
51	Martinez-QuintanillaJ, BhereD, HeidariP, HeD, MahmoodU, ShahK (2013). Therapeutic efficacy and fate of bimodal engineered stem cells in malignant brain tumors. Stem Cells, 31(8): 1706–1714 doi: 10.1002/stem.1355 pmid: 23389839
52	MarxJ (2008). Cancer biology.All in the stroma: cancer’s Cosa Nostra. Science, 320(5872): 38–41 doi: 10.1126/science.320.5872.38 pmid: 18388269
53	MatuskovaM, HlubinovaK, PastorakovaA, HunakovaL, AltanerovaV, AltanerC, KucerovaL (2010). HSV-tk expressing mesenchymal stem cells exert bystander effect on human glioblastoma cells. Cancer Lett, 290(1): 58–67 doi: 10.1016/j.canlet.2009.08.028 pmid: 19765892
54	MiZ, BhattacharyaS D, KimV M, GuoH, TalbotL J, KuoP C (2011). Osteopontin promotes CCL5-mesenchymal stromal cell-mediated breast cancer metastasis. Carcinogenesis, 32(4): 477–487 doi: 10.1093/carcin/bgr009 pmid: 21252118
55	MiZ, GuoH, RussellM B, LiuY, SullengerB A, KuoP C (2009). RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells. Mol Ther, 17(1): 153–161 doi: 10.1038/mt.2008.235 pmid: 18985031
56	MishraP J, MishraP J, HumeniukR, MedinaD J, AlexeG, MesirovJ P, GanesanS, GlodJ W, BanerjeeD (2008). Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res, 68(11): 4331–4339 doi: 10.1158/0008-5472.CAN-08-0943 pmid: 18519693
57	NasefA, MathieuN, ChapelA, FrickJ, FrançoisS, MazurierC, BoutarfaA, BouchetS, GorinN C, ThierryD, FouillardL (2007). Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation, 84(2): 231–237 doi: 10.1097/01.tp.0000267918.07906.08 pmid: 17667815
58	PatelS A, MeyerJ R, GrecoS J, CorcoranK E, BryanM, RameshwarP (2010). Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol, 184(10): 5885–5894 doi: 10.4049/jimmunol.0903143 pmid: 20382885
59	PeinadoH, AlečkovićM, LavotshkinS, MateiI, Costa-SilvaB, Moreno-BuenoG, Hergueta-RedondoM, WilliamsC, García-SantosG, GhajarC, Nitadori-HoshinoA, HoffmanC, BadalK, GarciaB A, CallahanM K, YuanJ, MartinsV R, SkogJ, KaplanR N, BradyM S, WolchokJ D, ChapmanP B, KangY, BrombergJ, LydenD (2012). Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med, 18(6): 883–891 doi: 10.1038/nm.2753 pmid: 22635005
60	PeterM E (2009). Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle, 8(6): 843–852 doi: 10.4161/cc.8.6.7907 pmid: 19221491
61	QiaoL, XuZ L, ZhaoT J, YeL H, ZhangX D (2008). Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling. Cancer Lett, 269(1): 67–77 doi: 10.1016/j.canlet.2008.04.032 pmid: 18571836
62	QuanteM, TuS P, TomitaH, GondaT, WangS S, TakashiS, BaikG H, ShibataW, DipreteB, BetzK S, FriedmanR, VarroA, TyckoB, WangT C (2011). Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell, 19(2): 257–272 doi: 10.1016/j.ccr.2011.01.020 pmid: 21316604
63	RappaG, MercapideJ, LoricoA (2012). Spontaneous formation of tumorigenic hybrids between breast cancer and multipotent stromal cells is a source of tumor heterogeneity. Am J Pathol, 180(6): 2504–2515 doi: 10.1016/j.ajpath.2012.02.020 pmid: 22542847
64	RenC, KumarS, ChandaD, ChenJ, MountzJ D, PonnazhaganS (2008a). Therapeutic potential of mesenchymal stem cells producing interferon-alpha in a mouse melanoma lung metastasis model. Stem Cells, 26(9): 2332–2338 doi: 10.1634/stemcells.2008-0084 pmid: 18617688
65	RenC, KumarS, ChandaD, KallmanL, ChenJ, MountzJ D, PonnazhaganS (2008b). Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model. Gene Ther, 15(21): 1446–1453 doi: 10.1038/gt.2008.101 pmid: 18596829
66	SageE K, KolluriK K, McNultyK, LourencoS D, KalberT L, OrdidgeK L, DaviesD, Gary LeeY C, GiangrecoA, JanesS M (2014). Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma. Thorax, doi: 10.1136/thoraxjnl-2013-204110 pmid: 24567297
67	SánchezL, Gutierrez-ArandaI, LigeroG, RubioR, Muñoz-LópezM, García-PérezJ L, RamosV, RealP J, BuenoC, RodríguezR, DelgadoM, MenendezP (2011). Enrichment of human ESC-derived multipotent mesenchymal stem cells with immunosuppressive and anti-inflammatory properties capable to protect against experimental inflammatory bowel disease. Stem Cells, 29(2): 251–262 doi: 10.1002/stem.569 pmid: 21732483
68	SasportasL S, KasmiehR, WakimotoH, HingtgenS, van de WaterJ A, MohapatraG, FigueiredoJ L, MartuzaR L, WeisslederR, ShahK (2009). Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA, 106(12): 4822–4827 doi: 10.1073/pnas.0806647106 pmid: 19264968
69	SeoK W, LeeH W, OhY I, AhnJ O, KohY R, OhS H, KangS K, YounH Y (2011a). Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell-based interferon-β gene therapy and cisplatin in a mouse melanoma model. Cytotherapy, 13(8): 944–955 doi: 10.3109/14653249.2011.584864 pmid: 21846298
70	SeoS H, KimK S, ParkS H, SuhY S, KimS J, JeunS S, SungY C (2011b). The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity. Gene Ther, 18(5): 488–495 doi: 10.1038/gt.2010.170 pmid: 21228885
71	ShangguanL, TiX, KrauseU, HaiB, ZhaoY, YangZ, LiuF (2012). Inhibition of TGF-β/Smad signaling by BAMBI blocks differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and abolishes their protumor effects. Stem Cells, 30(12): 2810–2819 doi: 10.1002/stem.1251 pmid: 23034983
72	ShimodaM, MellodyK T, OrimoA (2010). Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour progression. Semin Cell Dev Biol, 21(1): 19–25 doi: 10.1016/j.semcdb.2009.10.002 pmid: 19857592
73	ShinagawaK, KitadaiY, TanakaM, SumidaT, OnoyamaM, OhnishiM, OharaE, HigashiY, TanakaS, YasuiW, ChayamaK (2013). Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer. Int J Cancer, 132(4): 813–823 doi: 10.1002/ijc.27735 pmid: 22821812
74	SongC, LiG (2011). CXCR4 and matrix metalloproteinase-2 are involved in mesenchymal stromal cell homing and engraftment to tumors. Cytotherapy, 13(5): 549–561 doi: 10.3109/14653249.2010.542457 pmid: 21171825
75	SpaethE L, LabaffA M, TooleB P, KloppA, AndreeffM, MariniF C (2013). Mesenchymal CD44 expression contributes to the acquisition of an activated fibroblast phenotype via TWIST activation in the tumor microenvironment. Cancer Res, 73(17): 5347–5359 doi: 10.1158/0008-5472.CAN-13-0087 pmid: 23838935
76	StroncekD, BerlyneD, FoxB, GeeA, HeimfeldS, LindbladR, LoperK, McKennaD Jr, RooneyC, SabatinoM, WagnerE, WhitesideT, WoodD, Heath-MondoroT (2010). Developments in clinical cell therapy. Cytotherapy, 12(3): 425–428 doi: 10.3109/14653240903511952 pmid: 20078383
77	SuzukiK, SunR, OriguchiM, KanehiraM, TakahataT, ItohJ, UmezawaA, KijimaH, FukudaS, SaijoY (2011). Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Mol Med, 17(7-8): 579–587 doi: 10.2119/molmed.2010.00157 pmid: 21424106
78	TokarE J, DiwanB A, WaalkesM P (2010). Arsenic exposure transforms human epithelial stem/progenitor cells into a cancer stem-like phenotype. Environ Health Perspect, 118(1): 108–115 pmid: 20056578
79	Toledano FurmanN E, Lupu-HaberY, BronshteinT, KanetiL, LetkoN, WeinsteinE, BaruchL, MachlufM (2013). Reconstructed stem cell nanoghosts: a natural tumor targeting platform. Nano Lett, 13(7): 3248–3255 doi: 10.1021/nl401376w pmid: 23786263
80	UchiboriR, OkadaT, ItoT, UrabeM, MizukamiH, KumeA, OzawaK (2009). Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapy. J Gene Med, 11(5): 373–381 doi: 10.1002/jgm.1313 pmid: 19274675
81	VarnatF, DuquetA, MalerbaM, ZbindenM, MasC, GervazP, Ruiz i AltabaA (2009). Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med, 1(6-7): 338–351 doi: 10.1002/emmm.200900039 pmid: 20049737
82	ViswanathanS, KeatingA, DeansR, HemattiP, ProckopD, StroncekD F, StaceyG, WeissD J, MasonC, RaoM S (2014). Soliciting Strategies for Developing Cell-Based Reference Materials to Advance MSC Research and Clinical Translation. Stem Cells Dev: 140310064908006 doi: 10.1089/scd.2013.0591 pmid: 24422625
83	WangM L, PanC M, ChiouS H, ChenW H, ChangH Y, LeeO K, HsuH S, WuC W (2012). Oncostatin m modulates the mesenchymal-epithelial transition of lung adenocarcinoma cells by a mesenchymal stem cell-mediated paracrine effect. Cancer Res, 72(22): 6051–6064 doi: 10.1158/0008-5472.CAN-12-1568 pmid: 23139208
84	WuS, JuG Q, DuT, ZhuY J, LiuG H (2013). Microvesicles derived from human umbilical cord Wharton’s jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo. PLoS ONE, 8(4): e61366 doi: 10.1371/journal.pone.0061366 pmid: 23593475
85	WuY, ZhouB P (2010). Snail: More than EMT. Cell Adhes Migr, 4(2): 199–203 doi: 10.4161/cam.4.2.10943 pmid: 20168078
86	XinH, KanehiraM, MizuguchiH, HayakawaT, KikuchiT, NukiwaT, SaijoY (2007). Targeted delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells. Stem Cells, 25(7): 1618–1626 doi: 10.1634/stemcells.2006-0461 pmid: 17412895
87	XuM H, GaoX, LuoD, ZhouX D, XiongW, LiuG X (2014). EMT and acquisition of stem cell-like properties are involved in spontaneous formation of tumorigenic hybrids between lung cancer and bone marrow-derived mesenchymal stem cells. PLoS ONE, 9(2): e87893 doi: 10.1371/journal.pone.0087893 pmid: 24516569
88	XuS, MenuE, De BeckerA, Van CampB, VanderkerkenK, Van RietI (2012). Bone marrow-derived mesenchymal stromal cells are attracted by multiple myeloma cell-produced chemokine CCL25 and favor myeloma cell growth in vitro and in vivo. Stem Cells, 30(2): 266–279 doi: 10.1002/stem.787 pmid: 22102554

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