The secret role of microRNAs in cancer stem cell development and potential therapy: A Notch-pathway approach

Frontiers in Oncology

Volumn 4, Issue DEC, 2014, Pages

  Prokopi, Marianna ^a,b   Kousparou, Christina A ^a   Epenetos, Agamemnon A ^a,c  

^a Bank of Cyprus Group Oncology Centre   (Cyprus)

^b CYPRUS UNIVERSITY OF TECHNOLOGY   (Cyprus)

^c ST BARTHOLOMEW S HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; JAGGED1; MICRORNA; MICRORNA 1; MICRORNA 141; MICRORNA 143; MICRORNA 146A; MICRORNA 199 5P; MICRORNA 200; MICRORNA 200B; MICRORNA 200C; MICRORNA 34; MICRORNA 34A; MICRORNA 34B; MICRORNA 34C; NOTCH RECEPTOR; NOTCH1 RECEPTOR; NOTCH3 RECEPTOR; TRANSCRIPTION FACTOR HES 1; TRANSCRIPTION FACTOR ZEB1; UNCLASSIFIED DRUG; WNT PROTEIN;

ARTICLE; BREAST CANCER; CANCER GROWTH; CANCER PROGNOSIS; CANCER STEM CELL; CANCER THERAPY; CARCINOGENICITY; CELL DIFFERENTIATION; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; COLORECTAL CANCER; DOWN REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; PROSTATE CANCER; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TUMOR RECURRENCE; UPREGULATION;

EID: 84922560358     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2014.00389     Document Type: Article

References (71)

1. N. A. Lobo, Y. Shimono, D. Qian and M. F. Clarke: The biology of cancer stem cells, Annu Rev Cell Dev Biol 23, 675-699 (2007). 10.1146/annurev.cellbio.22.010305.104154 [doi]
2. C. S. Colmont, K. G. Harding, V. Piguet and G. K. Patel: Human skin cancer stem cells: a tale of mice and men, Exp Dermatol 21, 576-580 (2012). 10.1111/j.1600-0625.2012.01533.x [doi]
3. Z. Wang, Y. Li, S. Banerjee and F. H. Sarkar: Exploitation of the Notch signaling pathway as a novel target for cancer therapy, Anticancer Res 28, 3621-3630 (2008)
4. A. Joutel and E. Tournier-Lasserve: Notch signalling pathway and human diseases, Semin Cell Dev Biol 9, 619-625 (1998). S1084-9521(98)90261-0 [pii]
5. S. Stylianou, R. B. Clarke and K. Brennan: Aberrant activation of notch signaling in human breast cancer, Cancer Res 66, 1517-1525 (2006). 66/3/1517 [pii]
6. K. A. Wharton, K. M. Johansen, T. Xu and S. Artavanis-Tsakonas: Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats, Cell 43, 567-581 (1985). 0092-8674(85)90229-6 [pii]
7. S. Artavanis-Tsakonas, K. Matsuno and M. E. Fortini: Notch signaling, Science 268, 225-232 (1995)
8. R. Kopan and M. X. Ilagan: The canonical Notch signaling pathway: unfolding the activation mechanism, Cell 137, 216-233 (2009). 10.1016/j.cell.2009.03.045 [doi]
9. P. Ranganathan, K. L. Weaver and A. J. Capobianco: Notch signalling in solid tumours: a little bit of everything but not all the time, Nat Rev Cancer 11, 338-351 (2011). 10.1038/nrc3035 [doi]
10. T. C. Reynolds, S. D. Smith and J. Sklar: Analysis of DNA surrounding the breakpoints of chromosomal translocations involving the beta T cell receptor gene in human lymphoblastic neoplasms. Cell 50, 107-117 (1987)
11. Z. Wang, Y. Li, S. Banerjee and F. H. Sarkar: Emerging role of Notch in stem cells and cancer, Cancer Lett 279, 8-12 (2009). 10.1016/j.canlet.2008.09.030 [doi]
12. G. P. Dotto, Notch tumor suppressor function, Oncogene 27, 5115-5123 (2008). 10.1038/onc.2008.225 [doi]
13. M. Nicolas, A. Wolfer, K. Raj, J. A. Kummer, P. Mill, M. van Noort, C. C. Hui, H. Clevers, G. P. Dotto and F. Radtke: Notch1 functions as a tumor suppressor in mouse skin, Nat Genet 33, 416-421 (2003). 10.1038/ng1099 [doi]
14. M. Reedijk, S. Odorcic, L. Chang, H. Zhang, N. Miller, D. R. McCready, G. Lockwood and S. E. Egan: High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival, Cancer Res 65, 8530-8537 (2005). 65/18/8530 [pii]
15. S. Santagata, F. Demichelis, A. Riva, S. Varambally, M. D. Hofer, J. L. Kutok, R. Kim, J. Tang, J. E. Montie, A. M. Chinnaiyan, M. A. Rubin and J. C. Aster: JAGGED1 expression is associated with prostate cancer metastasis and recurrence, Cancer Res 64, 6854-6857 (2004). 64/19/6854 [pii]
16. Z. Wang, Y. Li, S. Banerjee, D. Kong, A. Ahmad, V. Nogueira, N. Hay and F. H. Sarkar: Down-regulation of Notch-1 and Jagged-1 inhibits prostate cancer cell growth, migration and invasion, and induces apoptosis via inactivation of Akt, mTOR, and NF-kappaB signaling pathways, J Cell Biochem 109, 726-736 (2010). 10.1002/jcb.22451 [doi]
17. M. Reedijk, S. Odorcic, H. Zhang, R. Chetty, C. Tennert, B. C. Dickson, G. Lockwood, S. Gallinger and S. E. Egan: Activation of Notch signaling in human colon adenocarcinoma, Int J Oncol 33, 1223-1229 (2008)
18. Z. Wang, S. Banerjee, Y. Li, K. M. Rahman, Y. Zhang and F. H. Sarkar: Down regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells, Cancer Res 66, 2778-2784 (2006). 66/5/2778 [pii]
19. K. A. Hassan, L. Wang, H. Korkaya, G. Chen, I. Maillard, D. G. Beer, G. P. Kalemkerian and M. S. Wicha: Notch pathway activity identifies cells with cancer stem cell-like properties and correlates with worse survival in lung adenocarcinoma, Clin Cancer Res 19, 1972-1980 (2013). 10.1158/1078-0432.CCR-12-0370 [doi]
20. K. Wang, X. Wu, J. Wang and J. Huang: Cancer stem cell theory: therapeutic implications for nanomedicine, Int J Nanomedicine 8, 899-908 (2013). 10.2147/IJN.S38641 [doi]
21. J. Grego-Bessa, J. Diez, L. Timmerman and J. L. de la Pompa: Notch and epithelial mesenchyme transition in development and tumor progression: another turn of the screw, Cell Cycle 3, 718-721 (2004). 949 [pii]
22. K. G. Leong, K. Niessen, I. Kulic, A. Raouf, C. Eaves, I. Pollet and A. Karsan: Jagged1- mediated Notch activation induces epithelial-to-mesenchymal transition through Slug induced repression of E-cadherin, J Exp Med 204, 2935-2948 (2007). jem.20071082 [pii]
23. J. P. Thiery, H. Acloque, R. Y. Huang and M. A. Nieto: Epithelial-mesenchymal transitions in development and disease, Cell 139, 871-890 (2009). 10.1016/j.cell.2009.11.007 [doi]
24. Y. Li, F. Guessous, Y. Zhang, C. Dipierro, B. Kefas, E. Johnson, L. Marcinkiewicz, J. Jiang, Y. Yang, T. D. Schmittgen, B. Lopes, D. Schiff, B. Purow and R. Abounader: MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes, Cancer Res 69, 7569-7576 (2009). 10.1158/0008-5472.CAN-09-0529 [doi]
25. L. Garzia, I. Andolfo, E. Cusanelli, N. Marino, G. Petrosino, D. De Martino, V. Esposito, A. Galeone, L. Navas, S. Esposito, S. Gargiulo, S. Fattet, V. Donofrio, G. Cinalli, A. Brunetti, L. D. Vecchio, P. A. Northcott, O. Delattre, M. D. Taylor, A. Iolascon and M. Zollo: MicroRNA-199b-5p impairs cancer stem cells through negative regulation of HES1 in medulloblastoma, PLoS One 4, e4998 (2009). 10.1371/journal.pone.0004998 [doi]
26. X. Cai, C. H. Hagedorn and B. R. Cullen: Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs, RNA 10, 1957-1966 (2004). rna.7135204 [pii]
27. L. He and G. J. Hannon: MicroRNAs: small RNAs with a big role in gene regulation, Nat Rev Genet 5, 522-531 (2004). 10.1038/nrg1379 [doi]
28. M. V. Iorio and C. M. Croce: Causes and consequences of microRNA dysregulation, Cancer J 18, 215-222 (2012). 10.1097/PPO.0b013e318250c001 [doi]
29. S. P. O'Hara, J. L. Mott, P. L. Splinter, G. J. Gores and N. F. LaRusso: MicroRNAs: key modulators of posttranscriptional gene expression, Gastroenterology 136, 17-25 (2009). 10.1053/j.gastro.2008.11.028 [doi]
30. G. Di Leva and C. M. Croce: miRNA profiling of cancer, Curr Opin Genet Dev 23, 3-11 (2013). 10.1016/j.gde.2013.01.004 [doi]
31. S. Deng, G. A. Calin, C. M. Croce, G. Coukos and L. Zhang: Mechanisms of microRNA deregulation in human cancer, Cell Cycle 7, 2643-2646 (2008). 6597 [pii]
32. G. A. Calin, C. Sevignani, C. D. Dumitru, T. Hyslop, E. Noch, S. Yendamuri, M. Shimizu, S. Rattan, F. Bullrich, M. Negrini and C. M. Croce: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers, Proc Natl Acad Sci U S A 101, 2999-3004 (2004). 10.1073/pnas.0307323101 [doi]
33. C. Roldo, E. Missiaglia, J. P. Hagan, M. Falconi, P. Capelli, S. Bersani, G. A. Calin, S. Volinia, C. G. Liu, A. Scarpa and C. M. Croce: MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior, J Clin Oncol 24, 4677-4684 (2006). JCO.2005.05.5194 [pii]
34. X. Pan, Z. X. Wang and R. Wang: MicroRNA-21: a novel therapeutic target in human cancer, Cancer Biol Ther 10, 1224-1232 (2010). 14252 [pii]
35. S. Bian and T. Sun: Functions of noncoding RNAs in neural development and neurological diseases, Mol Neurobiol 44, 359-373 (2011). 10.1007/s12035-011-8211-3 [doi]
36. G. A. Calin and C. M. Croce: MicroRNA signatures in human cancers, Nat Rev Cancer 6, 857-866 (2006). nrc1997 [pii]
37. S. M. Hammond, RNAi, microRNAs, and human disease, Cancer Chemother Pharmacol 58 Suppl 1, s63-8 (2006). 10.1007/s00280-006-0318-2 [doi]
38. P. J. Mishra and G. Merlino: MicroRNA reexpression as differentiation therapy in cancer, J Clin Invest 119, 2119-2123 (2009). 10.1172/JCI40107 [doi]
39. A. Cimmino, G. A. Calin, M. Fabbri, M. V. Iorio, M. Ferracin, M. Shimizu, S. E. Wojcik, R. I. Aqeilan, S. Zupo, M. Dono, L. Rassenti, H. Alder, S. Volinia, C. G. Liu, T. J. Kipps, M. Negrini and C. M. Croce: miR-15 and miR-16 induce apoptosis by targeting BCL2, Proc Natl Acad Sci U S A 102, 13944-13949 (2005). 0506654102 [pii]
40. G. A. Calin, C. D. Dumitru, M. Shimizu, R. Bichi, S. Zupo, E. Noch, H. Aldler, S. Rattan, M. Keating, K. Rai, L. Rassenti, T. Kipps, M. Negrini, F. Bullrich and C. M. Croce: Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia, Proc Natl Acad Sci U S A 99, 15524-15529 (2002). 10.1073/pnas.242606799 [doi]
41. L. He, X. He, L. P. Lim, E. de Stanchina, Z. Xuan, Y. Liang, W. Xue, L. Zender, J. Magnus, D. Ridzon, A. L. Jackson, P. S. Linsley, C. Chen, S. W. Lowe, M. A. Cleary and G. J. Hannon: A microRNA component of the p53 tumour suppressor network, Nature 447, 1130-1134 (2007). nature05939 [pii]
42. Q. Ji, X. Hao, M. Zhang, W. Tang, M. Yang, L. Li, D. Xiang, J. T. Desano, G. T. Bommer, D. Fan, E. R. Fearon, T. S. Lawrence and L. Xu: MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells, PLoS One 4, e6816 (2009). 10.1371/journal.pone.0006816 [doi]
43. Y. Li, F. Guessous, Y. Zhang, C. Dipierro, B. Kefas, E. Johnson, L. Marcinkiewicz, J. Jiang, Y. Yang, T. D. Schmittgen, B. Lopes, D. Schiff, B. Purow and R. Abounader: MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes, Cancer Res 69, 7569-7576 (2009). 10.1158/0008-5472.CAN-09-0529 [doi]
44. C. He, J. Xiong, X. Xu, W. Lu, L. Liu, D. Xiao and D. Wang: Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples, Biochem Biophys Res Commun 388, 35-40 (2009). 10.1016/j.bbrc.2009.07.101 [doi]
45. L. Poellinger and U. Lendahl: Modulating Notch signaling by pathway-intrinsic and pathway-extrinsic mechanisms, Curr Opin Genet Dev 18, 449-454 (2008). 10.1016/j.gde.2008.07.013 [doi]
46. Z. Wu, Y. Wu, Y. Tian, X. Sun, J. Liu, H. Ren, C. Liang, L. Song, H. Hu, L. Wang and B. Jiao: Differential effects of miR-34c-3p and miR-34c-5p on the proliferation, apoptosis and invasion of glioma cells, Oncol Lett 6, 1447-1452 (2013). 10.3892/ol.2013.1579 [doi]
47. Z. Wang, Y. Zhang, Y. Li, S. Banerjee, J. Liao and F. H. Sarkar: Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells, Mol Cancer Ther 5, 483-493 (2006). 5/3/483 [pii]
48. M. Kashat, L. Azzouz, S. H. Sarkar, D. Kong, Y. Li and F. H. Sarkar: Inactivation of AR and Notch-1 signaling by miR-34a attenuates prostate cancer aggressiveness, Am J Transl Res 4, 432-442 (2012)
49. S. Brabletz, K. Bajdak, S. Meidhof, U. Burk, G. Niedermann, E. Firat, U. Wellner, A. Dimmler, G. Faller, J. Schubert and T. Brabletz: The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells, EMBO J 30, 770-782 (2011). 10.1038/emboj.2010.349 [doi]
50. D. M. Vallejo, E. Caparros and M. Dominguez: Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells, EMBO J 30, 756-769 (2011). 10.1038/emboj.2010.358 [doi]
51. Z. Wang, S. Banerjee, A. Ahmad, Y. Li, A. S. Azmi, J. R. Gunn, D. Kong, B. Bao, S. Ali, J. Gao, R. M. Mohammad, L. Miele, M. Korc and F. H. Sarkar: Activated K-ras and INK4a/Arf deficiency cooperate during the development of pancreatic cancer by activation of Notch and NF-kappaB signaling pathways, PLoS One 6, e20537 (2011). 10.1371/journal.pone.0020537 [doi]
52. S. Ohashi, M. Natsuizaka, S. Naganuma, S. Kagawa, S. Kimura, H. Itoh, R. A. Kalman, M. Nakagawa, D. S. Darling, D. Basu, P. A. Gimotty, A. J. Klein-Szanto, J. A. Diehl, M. Herlyn and H. Nakagawa: A NOTCH3-mediated squamous cell differentiation program limits expansion of EMT-competent cells that express the ZEB transcription factors, Cancer Res 71, 6836-6847 (2011). 10.1158/0008-5472.CAN-11-0846 [doi]
53. P. de Antonellis, L. Liguori, A. Falanga, M. Carotenuto, V. Ferrucci, I. Andolfo, F. Marinaro, I. Scognamiglio, A. Virgilio, G. De Rosa, A. Galeone, S. Galdiero and M. Zollo: MicroRNA 199b-5p delivery through stable nucleic acid lipid particles (SNALPs) in tumorigenic cell lines, Naunyn Schmiedebergs Arch Pharmacol 386, 287-302 (2013). 10.1007/s00210-013-0837-4 [doi]
54. X. Wang, H. Lu, T. Li, L. Yu, G. Liu, X. Peng and J. Zhao: Kruppel-like factor 8 promotes tumorigenic mammary stem cell induction by targeting miR-146a, Am J Cancer Res 3, 356-373 (2013)
55. Z. Wang, Y. Li, A. Ahmad, A. S. Azmi, S. Banerjee, D. Kong and F. H. Sarkar: Targeting Notch signaling pathway to overcome drug resistance for cancer therapy, Biochim Biophys Acta 1806, 258-267 (2010). 10.1016/j.bbcan.2010.06.001 [doi]
56. S. Furukawa, Y. Kawasaki, M. Miyamoto, M. Hiyoshi, J. Kitayama and T. Akiyama: The miR-1-NOTCH3-Asef pathway is important for colorectal tumor cell migration, PLoS One 8, e80609 (2013). 10.1371/journal.pone.0080609 [doi]
57. J. M. Mosquera, A. Sboner, L. Zhang, C. L. Chen, Y. S. Sung, H. W. Chen, N. P. Agaram, D. Briskin, B. M. Basha, S. Singer, M. A. Rubin, T. Tuschl and C. R. Antonescu: Novel MIR143-NOTCH fusions in benign and malignant glomus tumors, Genes Chromosomes Cancer 52, 1075-1087 (2013). 10.1002/gcc.22102 [doi]
58. Y. Li, F. Guessous, Y. Zhang, C. Dipierro, B. Kefas, E. Johnson, L. Marcinkiewicz, J. Jiang, Y. Yang, T. D. Schmittgen, B. Lopes, D. Schiff, B. Purow and R. Abounader: MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes, Cancer Res 69, 7569-7576 (2009). 10.1158/0008-5472.CAN-09-0529 [doi]
59. R. T. Pang, C. O. Leung, T. M. Ye, W. Liu, P. C. Chiu, K. K. Lam, K. F. Lee and W. S. Yeung: MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis 31, 1037-1044 (2010). 10.1093/carcin/bgq066 [doi]
60. P. Bu, K. Y. Chen, J. H. Chen, L. Wang, J. Walters, Y. J. Shin, J. P. Goerger, J. Sun, M. Witherspoon, N. Rakhilin, J. Li, H. Yang, J. Milsom, S. Lee, W. Zipfel, M. M. Jin, Z. H. Gumus, S. M. Lipkin and X. Shen: A microRNA miR-34a-regulated bimodal switch targets Notch in colon cancer stem cells, Cell Stem Cell 12, 602-615 (2013). 10.1016/j.stem.2013.03.002 [doi]
61. A. Lujambio, G. A. Calin, A. Villanueva, S. Ropero, M. Sanchez-Cespedes, D. Blanco, L. M. Montuenga, S. Rossi, M. S. Nicoloso, W. J. Faller, W. M. Gallagher, S. A. Eccles, C. M. Croce and M. Esteller: A microRNA DNA methylation signature for human cancer metastasis, Proc Natl Acad Sci U S A 105, 13556-13561 (2008). 10.1073/pnas.0803055105 [doi]
62. Z. Wu, Y. Wu, Y. Tian, X. Sun, J. Liu, H. Ren, C. Liang, L. Song, H. Hu, L. Wang and B. Jiao: Differential effects of miR-34c-3p and miR-34c-5p on the proliferation, apoptosis and invasion of glioma cells, Oncol Lett 6, 1447-1452 (2013). 10.3892/ol.2013.1579 [doi]
63. Z. Wang, S. Banerjee, A. Ahmad, Y. Li, A. S. Azmi, J. R. Gunn, D. Kong, B. Bao, S. Ali, J. Gao, R. M. Mohammad, L. Miele, M. Korc and F. H. Sarkar: Activated K-ras and INK4a/Arf deficiency cooperate during the development of pancreatic cancer by activation of Notch and NF-kappaB signaling pathways, PLoS One 6, e20537 (2011). 10.1371/journal.pone.0020537 [doi]
64. Y. P. Yang, Y. Chien, G. Y. Chiou, J. Y. Cherng, M. L. Wang, W. L. Lo, Y. L. Chang, P. I. Huang, Y. W. Chen, Y. H. Shih, M. T. Chen and S. H. Chiou: Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI, Biomaterials 33, 1462-1476 (2012). 10.1016/j.biomaterials.2011.10.071 [doi]
65. J. Kota, R. R. Chivukula, K. A. O'Donnell, E. A. Wentzel, C. L. Montgomery, H. W. Hwang, T. C. Chang, P. Vivekanandan, M. Torbenson, K. R. Clark, J. R. Mendell and J. T. Mendell: Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model, Cell 137, 1005-1017 (2009). 10.1016/j.cell.2009.04.021 [doi]
66. J. Ratajczak, K. Miekus, M. Kucia, J. Zhang, R. Reca, P. Dvorak and M. Z. Ratajczak: Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery, Leukemia 20, 847-856 (2006). 2404132 [pii]
67. M. Prokopi, G. Pula, U. Mayr, C. Devue, J. Gallagher, Q. Xiao, C. M. Boulanger, N. Westwood, C. Urbich, J. Willeit, M. Steiner, J. Breuss, Q. Xu, S. Kiechl and M. Mayr: Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures, Blood 114, 723-732 (2009). 10.1182/blood-2009-02-205930 [doi]
68. K. J. Rayner and E. J. Hennessy: Extracellular communication via microRNA: lipid particles have a new message, J Lipid Res 54, 1174-1181 (2013). 10.1194/jlr.R034991 [doi]
69. M. Prokopi, A. Epenetos, A. Anayiotos, C. Pitsillides, K. Kapnisis and C. Kousparou: Therapeutic miRNAs targeted selectively to tumors by mesenchymal stem cell derived microparticles, Proceedings of the 105th Annual Meeting of the American Association for Cancer Research 74 (2014). 10.1158/1538-7445.AM2014-1977
70. L. J. Dai, M. R. Moniri, Z. R. Zeng, J. X. Zhou, J. Rayat and G. L. Warnock: Potential implications of mesenchymal stem cells in cancer therapy, Cancer Lett 305, 8-20 (2011). 10.1016/j.canlet.2011.02.012 [doi]
71. V. Fritz and C. Jorgensen: Mesenchymal stem cells: an emerging tool for cancer targeting and therapy, Curr Stem Cell Res Ther 3, 32-42 (2008)