One cell, multiple roles: Contribution of mesenchymal stem cells to tumor development in tumor microenvironment

Cell and Bioscience

Volumn 3, Issue 1, 2013, Pages

  Yang, Xue ^a,b   Hou, Jing ^a   Han, Zhipeng ^a   Wang, Ying ^b   Hao, Chong ^a   Wei, Lixin ^a   Shi, Yufang ^b  

^a SECOND MILITARY MEDICAL UNIVERSITY   (China)

^b SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

Mesenchymal stem cells (MSCs); Metastasis; Tumor growth; Tumor microenvironment

Indexed keywords

EID: 84879517225     PISSN: None     EISSN: 20453701     Source Type: Journal    
DOI: 10.1186/2045-3701-3-5     Document Type: Article

References (168)

1. Bianchi G, Borgonovo G, Pistoia V, Raffaghello L. Immunosuppressive cells and tumour microenvironment: focus on mesenchymal stem cells and myeloid derived suppressor cells. Histol Histopathol 2011, 26(7):941-951.
2. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997, 276(5309):71-74.
3. Granero-Molto F, Weis JA, Longobardi L, Spagnoli A. Role of mesenchymal stem cells in regenerative medicine: application to bone and cartilage repair. Expert Opin Biol Ther 2008, 8(3):255-268.
4. Salem HK, Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 2010, 28(3):585-596.
5. Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M, Takeda S, Ide C, Nabeshima Y. Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science 2005, 309(5732):314-317.
6. Bianco P, Robey PG, Simmons PJ. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2008, 2(4):313-319.
7. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284(5411):143-147.
8. Anjos-Afonso F, Bonnet D. Nonhematopoietic/endothelial SSEA-1+ cells define the most primitive progenitors in the adult murine bone marrow mesenchymal compartment. Blood 2007, 109(3):1298-1306.
9. Anker PS I, Scherjon SA, Kleijburg-van der Keur C, de Groot-Swings GM, Claas FH, Fibbe WE, Kanhai HH. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 2004, 22(7):1338-1345.
10. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001, 7(2):211-228.
11. Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M. Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 2002, 62(13):3603-3608.
12. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986, 315(26):1650-1659.
13. Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, et al. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 2005, 65(8):3307-3318.
14. Niess H, Bao Q, Conrad C, Zischek C, Notohamiprodjo M, Schwab F, Schwarz B, Huss R, Jauch KW, Nelson PJ, et al. Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissue-specific suicide gene expression suppresses growth of hepatocellular carcinoma. Ann Surg 2011, 254(5):767-774. discussion 774-765.
15. Hall B, Dembinski J, Sasser AK, Studeny M, Andreeff M, Marini F. Mesenchymal stem cells in cancer: tumor-associated fibroblasts and cell-based delivery vehicles. Int J Hematol 2007, 86(1):8-16.
16. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000, 100(1):57-70.
17. Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest 2011, 121(10):3804-3809.
18. Gabbiani G, Majno G. Dupuytren's contracture: fibroblast contraction? An ultrastructural study. Am J Pathol 1972, 66(1):131-146.
19. Silzle T, Randolph GJ, Kreutz M, Kunz-Schughart LA. The fibroblast: sentinel cell and local immune modulator in tumor tissue. Int J Cancer 2004, 108(2):173-180.
20. Philip M, Rowley DA, Schreiber H. Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol 2004, 14(6):433-439.
21. Huh JI, Calvo A, Stafford J, Cheung M, Kumar R, Philp D, Kleinman HK, Green JE. Inhibition of VEGF receptors significantly impairs mammary cancer growth in C3(1)/Tag transgenic mice through antiangiogenic and non-antiangiogenic mechanisms. Oncogene 2005, 24(5):790-800.
22. Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 2011, 17:1498-1503.
23. Shi Y, Su J, Roberts AI, Shou P, Rabson AB, Ren G. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol 2012, 33(3):136-143.
24. Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takashi S, Baik GH, Shibata W, Diprete B, Betz KS, et al. Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell 2011, 19(2):257-272.
25. Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 2004, 4(1):11-22.
26. Nicolini A, Carpi A, Rossi G. Cytokines in breast cancer. Cytokine Growth Factor Rev 2006, 17(5):325-337.
27. Mocellin S, Wang E, Marincola FM. Cytokines and immune response in the tumor microenvironment. J Immunother 2001, 24(5):392-407.
28. Obiri NI, Siegel JP, Varricchio F, Puri RK. Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast carcinoma cells. Clin Exp Immunol 1994, 95(1):148-155.
29. Salazar-Onfray F, Lopez MN, Mendoza-Naranjo A. Paradoxical effects of cytokines in tumor immune surveillance and tumor immune escape. Cytokine Growth Factor Rev 2007, 18(1-2):171-182.
30. Honma S, Shimodaira K, Shimizu Y, Tsuchiya N, Saito H, Yanaihara T, Okai T. The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells. Endocr J 2002, 49(3):371-377.
31. Knupfer H, Schmidt R, Stanitz D, Brauckhoff M, Schonfelder M, Preiss R. CYP2C and IL-6 expression in breast cancer. Breast 2004, 13(1):28-34.
32. Papac RJ. Spontaneous regression of cancer. Cancer Treat Rev 1996, 22(6):395-423.
33. D'Orazio TJ, Niederkorn JY. A novel role for TGF-beta and IL-10 in the induction of immune privilege. J Immunol 1998, 160(5):2089-2098.
34. Vitolo D, Gallo A, Ciocci L, Cicerone E, Baroni CD. Interleukin-12 related cytokine gene expression at a tissue level in carcinomas of the larynx. Eur Arch Otorhinolaryngol 2000, 257(5):290-294.
35. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY, Godfrey DI. Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 2000, 191(4):661-668.
36. Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Wolf SF, Gately MK. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 1993, 178(4):1223-1230.
37. Nanni P, Rossi I, De Giovanni C, Landuzzi L, Nicoletti G, Stoppacciaro A, Parenza M, Colombo MP, Lollini PL. Interleukin 12 gene therapy of MHC-negative murine melanoma metastases. Cancer Res 1998, 58(6):1225-1230.
38. Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S, Kleinman HK, Reaman GH, Tosato G. Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J Exp Med 1995, 182(1):155-162.
39. Fehniger TA, Suzuki K, Ponnappan A, VanDeusen JB, Cooper MA, Florea SM, Freud AG, Robinson ML, Durbin J, Caligiuri MA. Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells. J Exp Med 2001, 193(2):219-231.
40. Belardelli F, Ferrantini M, Proietti E, Kirkwood JM. Interferon-alpha in tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002, 13(2):119-134.
41. Khong HT, Restifo NP. Natural selection of tumor variants in the generation of "tumor escape" phenotypes. Nat Immunol 2002, 3(11):999-1005.
42. O'Hayre M, Salanga CL, Handel TM, Allen SJ. Chemokines and cancer: migration, intracellular signalling and intercellular communication in the microenvironment. Biochem J 2008, 409(3):635-649.
43. Nesbit M, Schaider H, Miller TH, Herlyn M. Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells. J Immunol 2001, 166(11):6483-6490.
44. Ishida T, Ishii T, Inagaki A, Yano H, Komatsu H, Iida S, Inagaki H, Ueda R. Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res 2006, 66(11):5716-5722.
45. Jordan JT, Sun W, Hussain SF, DeAngulo G, Prabhu SS, Heimberger AB. Preferential migration of regulatory T cells mediated by glioma-secreted chemokines can be blocked with chemotherapy. Cancer Immunol Immunother 2008, 57(1):123-131.
46. Mizukami Y, Kono K, Kawaguchi Y, Akaike H, Kamimura K, Sugai H, Fujii H. CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer. Int J Cancer 2008, 122(10):2286-2293.
47. Okada N, Gao JQ, Sasaki A, Niwa M, Okada Y, Nakayama T, Yoshie O, Mizuguchi H, Hayakawa T, Fujita T, et al. Anti-tumor activity of chemokine is affected by both kinds of tumors and the activation state of the host's immune system: implications for chemokine-based cancer immunotherapy. Biochem Biophys Res Commun 2004, 317(1):68-76.
48. Zhao M, Mueller BM, DiScipio RG, Schraufstatter IU. Akt plays an important role in breast cancer cell chemotaxis to CXCL12. Breast Cancer Res Treat 2008, 110(2):211-222.
49. Guiducci C, Di Carlo E, Parenza M, Hitt M, Giovarelli M, Musiani P, Colombo MP. Intralesional injection of adenovirus encoding CC chemokine ligand 16 inhibits mammary tumor growth and prevents metastatic-induced death after surgical removal of the treated primary tumor. J Immunol 2004, 172(7):4026-4036.
50. Gough M, Crittenden M, Thanarajasingam U, Sanchez-Perez L, Thompson J, Jevremovic D, Vile R. Gene therapy to manipulate effector T cell trafficking to tumors for immunotherapy. J Immunol 2005, 174(9):5766-5773.
51. Bonecchi R, Locati M, Mantovani A. Chemokines and cancer: a fatal attraction. Cancer Cell 19(4):434-435.
52. Braun SE, Chen K, Foster RG, Kim CH, Hromas R, Kaplan MH, Broxmeyer HE, Cornetta K. The CC chemokine CK beta-11/MIP-3 beta/ELC/Exodus 3 mediates tumor rejection of murine breast cancer cells through NK cells. J Immunol 2000, 164(8):4025-4031.
53. Fushimi T, Kojima A, Moore MA, Crystal RG. Macrophage inflammatory protein 3alpha transgene attracts dendritic cells to established murine tumors and suppresses tumor growth. J Clin Invest 2000, 105(10):1383-1393.
54. Cassier PA, Treilleux I, Bachelot T, Ray-Coquard I, Bendriss-Vermare N, Menetrier-Caux C, Tredan O, Goddard-Leon S, Pin JJ, Mignotte H, et al. Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer. BMC Cancer 11:213.
55. Ghadjar P, Coupland SE, Na IK, Noutsias M, Letsch A, Stroux A, Bauer S, Buhr HJ, Thiel E, Scheibenbogen C, et al. Chemokine receptor CCR6 expression level and liver metastases in colorectal cancer. J Clin Oncol 2006, 24(12):1910-1916.
56. Kimsey TF, Campbell AS, Albo D, Wilson M, Wang TN. Co-localization of macrophage inflammatory protein-3alpha (Mip-3alpha) and its receptor, CCR6, promotes pancreatic cancer cell invasion. Cancer J 2004, 10(6):374-380.
57. Murooka TT, Wong MM, Rahbar R, Majchrzak-Kita B, Proudfoot AE, Fish EN. CCL5-CCR5-mediated apoptosis in T cells: Requirement for glycosaminoglycan binding and CCL5 aggregation. J Biol Chem 2006, 281(35):25184-25194.
58. Vicari AP, Ait-Yahia S, Chemin K, Mueller A, Zlotnik A, Caux C. Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and immunological mechanisms. J Immunol 2000, 165(4):1992-2000.
59. Somasundaram R, Herlyn D. Chemokines and the microenvironment in neuroectodermal tumor-host interaction. Semin Cancer Biol 2009, 19(2):92-96.
60. Forster R, Davalos-Misslitz AC, Rot A. CCR7 and its ligands: balancing immunity and tolerance. Nat Rev Immunol 2008, 8(5):362-371.
61. Hoelzinger DB, Demuth T, Berens ME. Autocrine factors that sustain glioma invasion and paracrine biology in the brain microenvironment. J Natl Cancer Inst 2007, 99(21):1583-1593.
62. Karnoub AE, Weinberg RA. Chemokine networks and breast cancer metastasis. Breast Dis 2006, 26:75-85.
63. Shields JD, Emmett MS, Dunn DB, Joory KD, Sage LM, Rigby H, Mortimer PS, Orlando A, Levick JR, Bates DO. Chemokine-mediated migration of melanoma cells towards lymphatics--a mechanism contributing to metastasis. Oncogene 2007, 26(21):2997-3005.
64. Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, Dzuiba J, Van Damme J, Walz A, Marriott D, et al. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem 1995, 270(45):27348-27357.
65. Murakami T, Cardones AR, Finkelstein SE, Restifo NP, Klaunberg BA, Nestle FO, Castillo SS, Dennis PA, Hwang ST. Immune evasion by murine melanoma mediated through CC chemokine receptor-10. J Exp Med 2003, 198(9):1337-1347.
66. Gallagher PG, Bao Y, Prorock A, Zigrino P, Nischt R, Politi V, Mauch C, Dragulev B, Fox JW. Gene expression profiling reveals cross-talk between melanoma and fibroblasts: implications for host-tumor interactions in metastasis. Cancer Res 2005, 65(10):4134-4146.
67. Luan J, Shattuck-Brandt R, Haghnegahdar H, Owen JD, Strieter R, Burdick M, Nirodi C, Beauchamp D, Johnson KN, Richmond A. Mechanism and biological significance of constitutive expression of MGSA/GRO chemokines in malignant melanoma tumor progression. J Leukoc Biol 1997, 62(5):588-597.
68. Balentien E, Mufson BE, Shattuck RL, Derynck R, Richmond A. Effects of MGSA/GRO alpha on melanocyte transformation. Oncogene 1991, 6(7):1115-1124.
69. Owen JD, Strieter R, Burdick M, Haghnegahdar H, Nanney L, Shattuck-Brandt R, Richmond A. Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine beta and gamma proteins. Int J Cancer 1997, 73(1):94-103.
70. Ruiter D, Bogenrieder T, Elder D, Herlyn M. Melanoma-stroma interactions: structural and functional aspects. Lancet Oncol 2002, 3(1):35-43.
71. Salcedo R, Resau JH, Halverson D, Hudson EA, Dambach M, Powell D, Wasserman K, Oppenheim JJ. Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells. FASEB J 2000, 14(13):2055-2064.
72. Arenberg DA, Keane MP, DiGiovine B, Kunkel SL, Morris SB, Xue YY, Burdick MD, Glass MC, Iannettoni MD, Strieter RM. Epithelial-neutrophil activating peptide (ENA-78) is an important angiogenic factor in non-small cell lung cancer. J Clin Invest 1998, 102(3):465-472.
73. Ramjeesingh R, Leung R, Siu CH. Interleukin-8 secreted by endothelial cells induces chemotaxis of melanoma cells through the chemokine receptor CXCR1. FASEB J 2003, 17(10):1292-1294.
74. Schadendorf D, Moller A, Algermissen B, Worm M, Sticherling M, Czarnetzki BM. IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J Immunol 1993, 151(5):2667-2675.
75. Schaider H, Oka M, Bogenrieder T, Nesbit M, Satyamoorthy K, Berking C, Matsushima K, Herlyn M. Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8. Int J Cancer 2003, 103(3):335-343.
76. Belperio JA, Keane MP, Arenberg DA, Addison CL, Ehlert JE, Burdick MD, Strieter RM. CXC chemokines in angiogenesis. J Leukoc Biol 2000, 68(1):1-8.
77. Arenberg DA, Kunkel SL, Polverini PJ, Morris SB, Burdick MD, Glass MC, Taub DT, Iannettoni MD, Whyte RI, Strieter RM. Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J Exp Med 1996, 184(3):981-992.
78. Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, et al. Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med 1998, 187(12):2009-2021.
79. Liao F, Rabin RL, Yannelli JR, Koniaris LG, Vanguri P, Farber JM. Human Mig chemokine: biochemical and functional characterization. J Exp Med 1995, 182(5):1301-1314.
80. Luster AD, Leder P. IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo. J Exp Med 1993, 178(3):1057-1065.
81. Luster AD, Ravetch JV. Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med 1987, 166(4):1084-1097.
82. Sgadari C, Angiolillo AL, Tosato G. Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10. Blood 1996, 87(9):3877-3882.
83. Raman D, Baugher PJ, Thu YM, Richmond A. Role of chemokines in tumor growth. Cancer Lett 2007, 256(2):137-165.
84. Barbero S, Bajetto A, Bonavia R, Porcile C, Piccioli P, Pirani P, Ravetti JL, Zona G, Spaziante R, Florio T, et al. Expression of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 in human brain tumors and their involvement in glial proliferation in vitro. Ann N Y Acad Sci 2002, 973:60-69.
85. Sehgal A, Keener C, Boynton AL, Warrick J, Murphy GP. CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells. J Surg Oncol 1998, 69(2):99-104.
86. Graeber MB, Scheithauer BW, Kreutzberg GW. Microglia in brain tumors. Glia 2002, 40(2):252-259.
87. Burkle A, Niedermeier M, Schmitt-Graff A, Wierda WG, Keating MJ, Burger JA. Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B-cell chronic lymphocytic leukemia. Blood 2007, 110(9):3316-3325.
88. Lopez-Giral S, Quintana NE, Cabrerizo M, Alfonso-Perez M, Sala-Valdes M, De Soria VG, Fernandez-Ranada JM, Fernandez-Ruiz E, Munoz C. Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination. J Leukoc Biol 2004, 76(2):462-471.
89. Meijer J, Zeelenberg IS, Sipos B, Roos E. The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver. Cancer Res 2006, 66(19):9576-9582.
90. Frederick MJ, Henderson Y, Xu X, Deavers MT, Sahin AA, Wu H, Lewis DE, El-Naggar AK, Clayman GL. In vivo expression of the novel CXC chemokine BRAK in normal and cancerous human tissue. Am J Pathol 2000, 156(6):1937-1950.
91. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ. 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 2009, 5(1):54-63.
92. Salcedo R, Young HA, Ponce ML, Ward JM, Kleinman HK, Murphy WJ, Oppenheim JJ. Eotaxin (CCL11) induces in vivo angiogenic responses by human CCR3+ endothelial cells. J Immunol 2001, 166(12):7571-7578.
93. Bernardini G, Spinetti G, Ribatti D, Camarda G, Morbidelli L, Ziche M, Santoni A, Capogrossi MC, Napolitano M. I-309 binds to and activates endothelial cell functions and acts as an angiogenic molecule in vivo. Blood 2000, 96(13):4039-4045.
94. Slettenaar VI, Wilson JL. The chemokine network: a target in cancer biology?. Adv Drug Deliv Rev 2006, 58(8):962-974.
95. Shulby SA, Dolloff NG, Stearns ME, Meucci O, Fatatis A. CX3CR1-fractalkine expression regulates cellular mechanisms involved in adhesion, migration, and survival of human prostate cancer cells. Cancer Res 2004, 64(14):4693-4698.
96. Maione TE, Gray GS, Petro J, Hunt AJ, Donner AL, Bauer SI, Carson HF, Sharpe RJ. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science 1990, 247(4938):77-79.
97. Sharpe RJ, Byers HR, Scott CF, Bauer SI, Maione TE. Growth inhibition of murine melanoma and human colon carcinoma by recombinant human platelet factor 4. J Natl Cancer Inst 1990, 82(10):848-853.
98. Sgadari C, Angiolillo AL, Cherney BW, Pike SE, Farber JM, Koniaris LG, Vanguri P, Burd PR, Sheikh N, Gupta G, et al. Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo. Proc Natl Acad Sci USA 1996, 93(24):13791-13796.
99. Addison CL, Arenberg DA, Morris SB, Xue YY, Burdick MD, Mulligan MS, Iannettoni MD, Strieter RM. The CXC chemokine, monokine induced by interferon-gamma, inhibits non-small cell lung carcinoma tumor growth and metastasis. Hum Gene Ther 2000, 11(2):247-261.
100. Lange C, Togel F, Ittrich H, Clayton F, Nolte-Ernsting C, Zander AR, Westenfelder C. Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. Kidney Int 2005, 68(4):1613-1617.
101. Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 2005, 33(2):145-152.
102. Phinney DG, Isakova I. Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 2005, 11(10):1255-1265.
103. Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, Sato T, Miyanishi K, Takayama T, Takahashi M, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 2005, 106(2):756-763.
104. Natsu K, Ochi M, Mochizuki Y, Hachisuka H, Yanada S, Yasunaga Y. Allogeneic bone marrow-derived mesenchymal stromal cells promote the regeneration of injured skeletal muscle without differentiation into myofibers. Tissue Eng 2004, 10(7-8):1093-1112.
105. Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 2005, 111(2):150-156.
106. Komarova S, Roth J, Alvarez R, Curiel DT, Pereboeva L. Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor. J Ovarian Res 2010, 3:12.
107. Gao H, Priebe W, Glod J, Banerjee D. Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium. Stem Cells 2009, 27(4):857-865.
108. Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, Noel D, Jorgensen C. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003, 102(10):3837-3844.
109. Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells 2006, 24(4):1030-1041.
110. Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F. Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther 2008, 15(10):730-738.
111. Li X, Lu Y, Huang W, Xu H, Chen X, Geng Q, Fan H, Tan Y, Xue G, Jiang X. In vitro effect of adenovirus-mediated human Gamma Interferon gene transfer into human mesenchymal stem cells for chronic myelogenous leukemia. Hematol Oncol 2006, 24(3):151-158.
112. Chen XC, Wang R, Zhao X, Wei YQ, Hu M, Wang YS, Zhang XW, Zhang R, Zhang L, Yao B, et al. Prophylaxis against carcinogenesis in three kinds of unestablished tumor models via IL12-gene-engineered MSCs. Carcinogenesis 2006, 27(12):2434-2441.
113. Kucerova L, Altanerova V, Matuskova M, Tyciakova S, Altaner C. Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy. Cancer Res 2007, 67(13):6304-6313.
114. Xin H, Kanehira M, Mizuguchi H, Hayakawa T, Kikuchi T, Nukiwa T, Saijo Y. Targeted delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells. Stem Cells 2007, 25(7):1618-1626.
115. Kanehira M, Xin H, Hoshino K, Maemondo M, Mizuguchi H, Hayakawa T, Matsumoto K, Nakamura T, Nukiwa T, Saijo Y. Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells. Cancer Gene Ther 2007, 14(11):894-903.
116. Stoff-Khalili MA, Rivera AA, Mathis JM, Banerjee NS, Moon AS, Hess A, Rocconi RP, Numnum TM, Everts M, Chow LT, et al. Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma. Breast Cancer Res Treat 2007, 105(2):157-167.
117. Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M, Bekele BN, Champlin RE, Andreeff M. Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 2004, 96(21):1593-1603.
118. Aboody KS, Najbauer J, Danks MK. Stem and progenitor cell-mediated tumor selective gene therapy. Gene Ther 2008, 15(10):739-752.
119. Nakamura K, Ito Y, Kawano Y, Kurozumi K, Kobune M, Tsuda H, Bizen A, Honmou O, Niitsu Y, Hamada H. Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Ther 2004, 11(14):1155-1164.
120. Grisendi G, Bussolari R, Cafarelli L, Petak I, Rasini V, Veronesi E, De Santis G, Spano C, Tagliazzucchi M, Barti-Juhasz H, et al. Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res 2010, 70(9):3718-3729.
121. Loebinger MR, Eddaoudi A, Davies D, Janes SM. Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res 2009, 69(10):4134-4142.
122. Menon LG, Kelly K, Yang HW, Kim SK, Black PM, Carroll RS. Human bone marrow-derived mesenchymal stromal cells expressing S-TRAIL as a cellular delivery vehicle for human glioma therapy. Stem Cells 2009, 27(9):2320-2330.
123. Sasportas LS, Kasmieh R, Wakimoto H, Hingtgen S, van de Water JA, Mohapatra G, Figueiredo JL, Martuza RL, Weissleder R, Shah K. Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA 2009, 106(12):4822-4827.
124. Niess H, Bao Q, Conrad C, Zischek C, Notohamiprodjo M, Schwab F, Schwarz B, Huss R, Jauch KW, Nelson PJ, et al. Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissue-specific suicide gene expression suppresses growth of hepatocellular carcinoma. Ann Surg 2011, 254(5):767-774. discussion 774-765.
125. Nomura T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Neuroscience 2005, 136(1):161-169.
126. Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Ishii K, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y, et al. Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model. Mol Ther 2005, 11(1):96-104.
127. Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y, Kato K, et al. BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model. Mol Ther 2004, 9(2):189-197.
128. Ishikawa T, Terai S, Urata Y, Marumoto Y, Aoyama K, Sakaida I, Murata T, Nishina H, Shinoda K, Uchimura S, et al. Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes. Cell Tissue Res 2006, 323(2):221-231.
129. Lu Z, Hu X, Zhu C, Wang D, Zheng X, Liu Q. Overexpression of CNTF in Mesenchymal Stem Cells reduces demyelination and induces clinical recovery in experimental autoimmune encephalomyelitis mice. J Neuroimmunol 2009, 206(1-2):58-69.
130. Lu ZQ, Hu XQ, Zhu CS, Zheng XP, Wan DJ, Liu RY, Huang BJ, Huang WL. Bone marrow stromal cells transfected with ciliary neurotrophic factor gene ameliorates the symptoms and inflammation in C57BL/6 mice with experimental allergic encephalomyelitis. Nan Fang Yi Ke Da Xue Xue Bao 2009, 29(12):2355-2361.
131. Zhao MZ, Nonoguchi N, Ikeda N, Watanabe T, Furutama D, Miyazawa D, Funakoshi H, Kajimoto Y, Nakamura T, Dezawa M, et al. Novel therapeutic strategy for stroke in rats by bone marrow stromal cells and ex vivo HGF gene transfer with HSV-1 vector. J Cereb Blood Flow Metab 2006, 26(9):1176-1188.
132. Aquino JB, Bolontrade MF, Garcia MG, Podhajcer OL, Mazzolini G. Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma. Gene Ther 2010, 17(6):692-708.
133. Doering CB. Retroviral modification of mesenchymal stem cells for gene therapy of hemophilia. Methods Mol Biol 2008, 433:203-212.
134. Xu WT, Bian ZY, Fan QM, Li G, Tang TT. Human mesenchymal stem cells (hMSCs) target osteosarcoma and promote its growth and pulmonary metastasis. Cancer Lett 2009, 281(1):32-41.
135. Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, Cao W, Han C, Chen Y. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol 2006, 80(3):267-274.
136. Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B, Andreeff M, Marini F. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One 2009, 4(4):e4992.
137. Khakoo AY, Pati S, Anderson SA, Reid W, Elshal MF, Rovira II, Nguyen AT, Malide D, Combs CA, Hall G, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma. J Exp Med 2006, 203(5):1235-1247.
138. Djouad F, Bony C, Apparailly F, Louis-Plence P, Jorgensen C, Noel D. Earlier onset of syngeneic tumors in the presence of mesenchymal stem cells. Transplantation 2006, 82(8):1060-1066.
139. Han Z, Jing Y, Zhang S, Liu Y, Shi Y, Wei L. The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth. Cell Biosci 2(1):8.
140. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008, 2(2):141-150.
141. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006, 107(1):367-372.
142. Patel SA, Dave MA, Murthy RG, Helmy KY, Rameshwar P. Metastatic breast cancer cells in the bone marrow microenvironment: novel insights into oncoprotection. Oncol Rev 5(2):93-102.
143. Sanchez CG, Penfornis P, Oskowitz AZ, Boonjindasup AG, Cai DZ, Dhule SS, Rowan BG, Kelekar A, Krause DS, Pochampally RR. Activation of autophagy in mesenchymal stem cells provides tumor stromal support. Carcinogenesis 32(7):964-972.
144. Sanchez C, Oskowitz A, Pochampally RR. Epigenetic reprogramming of IGF1 and leptin genes by serum deprivation in multipotential mesenchymal stromal cells. Stem Cells 2009, 27(2):375-382.
145. Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, Prockop DJ. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PLoS One 2007, 2(5):e416.
146. 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):2363-2370.
147. 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):2179-2184.
148. Dias S, Shmelkov SV, Lam G, Rafii S. VEGF(165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition. Blood 2002, 99(7):2532-2540.
149. Konig A, Menzel T, Lynen S, Wrazel L, Rosen A, Al-Katib A, Raveche E, Gabrilove JL. 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):258-265.
150. Brogi E, Wu T, Namiki A, Isner JM. Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. Circulation 1994, 90(2):649-652.
151. 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):2655-2663.
152. Stamler JS. Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell 1994, 78(6):931-936.
153. Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nunez G, et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 1999, 10(1):105-115.
154. Li ZW, Dalton WS. Tumor microenvironment and drug resistance in hematologic malignancies. Blood Rev 2006, 20(6):333-342.
155. Tsukamoto S, Honoki K, Fujii H, Tohma Y, Kido A, Mori T, Tsujiuchi T, Tanaka Y. Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model. Int J Oncol 40(1):163-169.
156. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007, 449(7162):557-563.
157. Shinagawa K, Kitadai Y, Tanaka M, Sumida T, Kodama M, Higashi Y, Tanaka S, Yasui W, Chayama K. Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer 127(10):2323-2333.
158. Martin FT, Dwyer RM, Kelly J, Khan S, Murphy JM, Curran C, Miller N, Hennessy E, Dockery P, Barry FP, 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 124(2):317-326.
159. Yoo YA, Kang MH, Kim BS, Kim JS, Seo JH. Sustained co-cultivation with human placenta-derived MSCs enhances ALK5/Smad3 signaling in human breast epithelial cells, leading to EMT and differentiation. Differentiation 2009, 77(5):450-461.
160. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 2001, 29(2):117-129.
161. Wanami LS, Chen HY, Peiro S, Garcia de Herreros A, Bachelder RE. Vascular endothelial growth factor-A stimulates Snail expression in breast tumor cells: implications for tumor progression. Exp Cell Res 2008, 314(13):2448-2453.
162. Jing Y, Han Z, Zhang S, Liu Y, Wei L. Epithelial-mesenchymal transition in tumor microenvironment. Cell Biosci 2011, 1:29.
163. Liu S, Ginestier C, Ou SJ, Clouthier SG, Patel SH, Monville F, Korkaya H, Heath A, Dutcher J, Kleer CG, et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 2011, 71(2):614-624.
164. Abarrategi A, Marinas-Pardo L, Mirones I, Rincon E, Garcia-Castro J. Mesenchymal niches of bone marrow in cancer. Clin Transl Oncol 2011, 13(9):611-616.
165. McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S, Cabrera L, Keller E, McCauley L, Cho KR, et al. Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Invest 2011, 121(8):3206-3219.
166. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005, 438(7069):820-827.
167. Bergfeld SA, DeClerck YA. Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev 2010, 29(2):249-261.
168. Chantrain CF, Feron O, Marbaix E, DeClerck YA. Bone marrow microenvironment and tumor progression. Cancer Microenviron 2008, 1(1):23-35.