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充质干细胞是中胚层发育的早期细胞,是一种未分化细胞, 广泛存在于已分化组织中。间充质干细胞(mesenchymal stem cells, MSCs)是一种无造血功能的干细胞, 广泛存在于胎儿和成人的各种组织和脏器中, 其中骨髓中的含量最多。MSCs具有较强的增殖能力及多项分化潜能,可分化为成纤维细胞、成骨细胞、成软骨细胞、脂肪细胞和肺泡上皮细胞等,在心血管系统、神经系统、呼吸系统和创伤等领域得到广泛应用。MSCs不仅能转化成恶性肿瘤细胞,并且对肿瘤的发生发展的过程也有影响。MSCs在肿瘤局部的作用可表现为促进肿瘤生长,发挥免疫抑制作用,抑制肿瘤凋亡,刺激血管生成、增殖,促进肿瘤细胞的转移。而MSCs具有向肿瘤组织趋化迁移的特性,可以将MSCs作为肿瘤治疗的载体,通过病毒载体将各种对肿瘤有抑制作用的基因转染到MSCs来达到抑制甚至杀死肿瘤的作用,因此MSCs与肿瘤的关系成为近期研究热点。本文就MSCs生物学特性、肿瘤趋向性及与肿瘤的关系等作一综述。
间充质干细胞与肿瘤关系的研究进展
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[1] HO PJ, YEN ML, YET SF, et al.Current applications of humanpluripotent stem cells:possibilities and challenges[J].Cell Transplant, 2012, 21(5):801. doi: 10.3727/096368911X627507 [2] DOMINICI M, LE B K, MUELLER I, et al.The internationalsociety for cellular therapy positonstat ement[J].Cytotherapy, 2006, 8(4):315. doi: 10.1080/14653240600855905 [3] GRONTHOS S, ZANNETTINO AC, HAY SJ, et al.Molecular and cellular characterisation of highly purifiedstromal stem cells derived from human bone marrow[J].J Cell Sci, 2003, 116(Pt 9):1827. [4] GRIFFITHS MJ, BONNET D, JANES SM.Stem cells of the alveolarepithelium[J].Lancet, 2005, 366(9481):249. doi: 10.1016/S0140-6736(05)66916-4 [5] MIMEAULT M, HAUKE R, BATRA SK.Stem cells:a revolution intherapeutics-recent advances in stem cell biology and theirtherapeutic applications in regenerative medicine and cancertherapies[J].Clin Pharmacol Ther, 2007, 82(3):252. doi: 10.1038/sj.clpt.6100301 [6] KERPEDJIEVA SS, KIM DS, BARBEAU DJ, et al.EGFR ligands drive multi-potential stromal cells to produce multiple growth factors and cytokines viaearly growth response-1[J].Stem Cells Dev, 2012, 21:2541. doi: 10.1089/scd.2011.0711 [7] SIEGEL G, KLUBA T, HERMANUTZ-KLEIN U, et al.Phe-notype, donor age and gender affect function of human bone marrow-derivedmesenchymal stromal cells[J].BMC Med, 2013, 11:146. doi: 10.1186/1741-7015-11-146 [8] BARTHOLOMEW A, STURGEEN C, SIATKA SM, et al.Mesenchymalstem cells suppress lym phocyte proliferation in vitro and prolongskin graft survival in vivo[J].Exp Hematol, 2002, 30(1):42. doi: 10.1016/S0301-472X(01)00769-X [9] GEBLER A, ZABEL O, SELIGER B.The immunomodulatory capacity of mesenchymal stemcells[J].Trends Mol Med, 2012, 18(2):128. doi: 10.1016/j.molmed.2011.10.004 [10] PARAISO KH, SMALLEY KS.Fibroblast-mediated drug resistance in cancer[J].Biochem Pharmacol, 2013, 85:1033. doi: 10.1016/j.bcp.2013.01.018 [11] WOOD SL, PERNEMALM M, CROSBIE PA, et al.The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potentialtherapeutic targets[J].Cancer Treat Rev, 2013(13):205. [12] NAKAMIZO A, MARINI F, AMANO T.Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas[J].Cancer Res, 2005, 65(8):3307. doi: 10.1158/0008-5472.CAN-04-1874 [13] KIDD S, SPAETH E, WATSON K, et al.Origins of thetumor microenvironment:quantitative assessment of adipose-derivedand bone marrow-derived stroma[J].PLoS One, 2012, 7(2):e30563. doi: 10.1371/journal.pone.0030563 [14] ESPOSITO M, KANG Y.Targeting tumor-stromal interactions in bone metastasis[J].Pharmacol Ther, 2014, 141:222. doi: 10.1016/j.pharmthera.2013.10.006 [15] UCHIBORI R, TSUKAHARA T, MIZUGUCHI H, et al.NF-κB activity regulates mesenchymal stem cell accumulation attumor sites[J].Cancer Res, 2013, 73(1):364. [16] TEO GS, ANKRUM JA, MARTINELLI R, et al.Mesenchymal stem cells transmigrate between and directly throughtumor necrosis factor-alpha-activated endothelial cells via bothleukocyte-like and novel mechanisms[J].Stem Cells, 2012, 30(11):2472. doi: 10.1002/stem.v30.11 [17] LIU S, GINESTIER C, OU SJ, et al.Breastcancer stem cells are regulated by mesenchymal stem cells throughcytokine networks[J].Cancer Res, 2011, 71(2):614. doi: 10.1158/0008-5472.CAN-10-0538 [18] LIN G, YANG R, BANIE L, et al.Effects oftransplantation of adipose tissue-derived stem cells on prostate tumor[J].Rostate, 2010, 70(10):1066. doi: 10.1002/pros.v70:10 [19] GAO H, PRIEBEW, GLOD J, et al.Activation of signal transducers andactivators of transcription 3 and focal adhesion kinase by stromal cell-derivedfactor 1 is required for migration of human mesenchymal stem cells inresponse to tumor cell-conditioned medium[J].Stem Cells, 2009, 27(4):857. doi: 10.1002/stem.v27:4 [20] SHI M, LI J, LIAO L, et al.Regulation of CXCR4 expressionin human mesenchymal stem cells by cytokine treatment:role in homingefficiency in NOD/SCID mice[J].Haematologica, 2007, 92(7):897. doi: 10.3324/haematol.10669 [21] CHATURVEDI P, GILKES DM, WONG CC, et al.Hypoxia-inducible factor-dependent breast cancer-mesenchymal stemcell bidirectional signaling promotes metastasis[J].J Clin Invest, 2013, 123(1):189. [22] TRAPANI J, SMTH MJ.Functional significance of the perforin/granzyme cell death pathway[J].Nat Rev Immunol, 2002, 2(10):735. doi: 10.1038/nri911 [23] MOHSENY A, XIAO W, CARVALHO R, et al.An osteosarcoma zebrafishmodel implicates Mmp-19 and Ets-1 as well as reduced hostimmune response in angiogenesis and migration[J].Pathol, 2012, 227(2):245. [24] CHANG AI, SCHWERTSCHKOW AH, NOLTA JA, et al.Involvement of mesenchymal stem cells in cancer progression and metastases[J].Curr Cancer Drug Targets, 2015, 15(2):88. doi: 10.2174/1568009615666150126154151 [25] PATEL A, MEYER J, GRECO J, et al.Mesenchymal stem cells protect breast cancer cellsthrough regulatory T cells:role of mesenchymal stem cell-derived TGF-β[J].J Immunol, 2010, 184(10):5885. doi: 10.4049/jimmunol.0903143 [26] GRUENLOH W, KAMBAL A, SONDERGAARD C, et al.Characterization and in vivo testing of mesenchymal stem cellsderived from human embryonic stem cells[J].Tissue Eng Part A, 2011, 17(11/12):1517. [27] LIEW A, O'BRIEN T.Therapeutic potential for mesenchymal stemcell transplantation in critical limb ischemia[J].Stem Cell Res Ther, 2012, 3(4):28. doi: 10.1186/scrt119 [28] COMŞA S CIUCULESCU F, RAICA M.Mesenchymal stem cell-tumor cellcooperation in breast cancer vasculogenesis[J].Mol Med Rep, 2012, 5(5):1175. [29] HUNG C, POCHAMPALLY R, CHEN S.Angiogenic effects of human multipotent stromal cellconditioned medium activate the PI3K-Akt pathway in hypoxicendothelial cells to inhibit apoptosis, increase survival, andstimulate angiogenesis[J].Stem Cells, 2007, 25(9):2363. doi: 10.1634/stemcells.2006-0686 [30] LIU Y, HANM Z, ZHANG S, et al.Effects of inflammatory factors onmesenchymal stem cells and their role in the promotion of tumorangiogenesis in colon cancer[J].Biol Chem, 2011, 286(28):25007. doi: 10.1074/jbc.M110.213108 [31] MUEHLBERG FL, SONG YH, KROHN A, et al.Tissue-resident stem cells promote breast cancer growth and metastasis[J].Carcinogenesis, 2009, 30(4):589. doi: 10.1093/carcin/bgp036 [32] SHINAGAWA K, KITADAI Y, TANAKA M, et al.Mesenchymal stem cells enhance growth and metastasis of coloncancer[J].Int J Cancer, 2010, 127(10):2323. doi: 10.1002/ijc.25440 [33] IWAMOTO S, MIHARA K, DOWNING JR, et al.Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase[J].Clin Invest, 2007, 117(4):1049. doi: 10.1172/JCI30235 [34] VIANELLO F, TISATO V, LYMPERI S, et al.Bone marrow mesenchymal stromal cells non-selectively protect chronic myeloid leukemia cells from imatinib-induced apoptosis via the CXCR4/CXCL12 axis[J].Haematologica, 2010, 95(7):1081. doi: 10.3324/haematol.2009.017178 [35] BALAKRISHNAN K, BURGER JA, QUIROGA MP, et al.Influence of bone marrow stromal microenvironment on forodesine-induced responses in CLL primary cells[J].Blood, 2010, 116(7):1083. doi: 10.1182/blood-2009-10-246199 [36] KARNOUB AE, DASH AB, RICHARDSON AL, et al.Mesenchymal stem cells within tumour stroma promote breast cancer metastasis[J].Nature, 2007, 449(7162):557. doi: 10.1038/nature06188 [37] ZHOU S, ZHOU ZJ, HU ZQ, et al.CXCR2/CXCL5 axis contributes to epithelial-mesenchymal transition of HCC cells through activating PI3K/Akt/GSK-3β/snail signaling[J].Cancer Lett, 2015, 358(2):124. doi: 10.1016/j.canlet.2014.11.044 [38] YANG J, MANI SA, DONAHER JL, et al.Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis[J].Cell, 2004, 117(7):927. doi: 10.1016/j.cell.2004.06.006 [39] CHATURVEDI P, GILKES DM, TAKANO N, et al.Hypoxiainducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment[J].Proc Natl Acad Sci USA, 2014, 111(20):E2120. doi: 10.1073/pnas.1406655111 [40] CHATURVEDI P, GILKES DM, WONG C, et al.Hypoxia-inducible factor-dependent breast cancermesenchymal stem cell bidirectional signaling promotes metastasis[J].Clin Invest, 2013, 123(20):189. [41] JING Y, HAN Z, LIU Y, et al.Mesenchymal stem cellsin inflammation microenvironment accelerates hepatocellular carcinomametastasis by inducing epithelial-mesenchymal transition[J].PLoS One, 2012, 7(8):e43272. doi: 10.1371/journal.pone.0043272 [42] SHIN SY, NAM JS, LIM Y, et al.TNFalpha-exposed bone marrow-derived mesenchymal stem cells promote locomotion of MDA-MB-231 breastcancer cells through transcriptional activation of CXCR3 ligandchemokines[J].Biol Chem, 2010, 285(40):30731. doi: 10.1074/jbc.M110.128124
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