The treatment of breast cancer, the most common malignancy among women worldwide, remains puzzling partly due to the resistance to therapeutics, which associates with the heterogeneity of case clinical presentations, and limits in the current understanding of the pathogenesis of solid cancers. Notably, it remains unclear: (i) whether breast cancer starts strictly as a local disease before metastasizing to the lymph nodes and distant organs, i.e. if cancer initiating cells are local cells that have undergone epithelial to mesenchymal transition; (ii) or if breast cancer is intrinsically a systemic disease started by malfunctioning circulating mesenchymal stem cells (MSCs) infiltrating the breast stroma to start tumorigenesis. Such limits in our understanding of breast cancer biology have been slowing the development of MSC-based therapies exploiting the ability of these cells to home into tumorigenic sites, kill cancer cells, stop neoangiogenesis, and repair damaged tissues, as well as therapeutic approaches using these cells as vehicle for gene therapy and for delivering anticancer therapeutics, which are potential game changing therapeutic approaches, particularly in currently incurable cancers and intractable cases. Major drawbacks to MSC-based therapy implementation and use in breast cancer are herein briefly discussed.
| Published in |
International Journal of Biomedical Science and Engineering (Volume 2, Issue 6-1)
This article belongs to the Special Issue Cancer Research |
| DOI | 10.11648/j.ijbse.s.2014020601.13 |
| Page(s) | 20-24 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2015. Published by Science Publishing Group |
Stem Cells, Breast Cancer, Microenvironment, Signaling Pathways, Therapy, Therapeutic Resistance
| [1] | Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int.J.Cancer 2001; 94:153-156 |
| [2] | Roukos DH, Murray S, Briasoulis E. Molecular genetic tools shape a roadmap towards a more accurate prognostic prediction and personalized management of cancer. Cancer Biol.Ther. 2007; 6:308-312 |
| [3] | Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J.Clin.Invest 2011; 121:2750-2767 |
| [4] | Liu ZJ, Zhuge Y, Velazquez OC. Trafficking and differentiation of mesenchymal stem cells. J.Cell Biochem. 2009; 106:984-991 |
| [5] | Duenas F, Becerra V, Cortes Y, Vidal S, Saenz L, Palomino J, De Los RM, Peralta OA. Hepatogenic and neurogenic differentiation of bone marrow mesenchymal stem cells from abattoir-derived bovine fetuses. BMC.Vet.Res. 2014; 10:154 |
| [6] | Galderisi U, Giordano A, Paggi MG. The bad and the good of mesenchymal stem cells in cancer: Boosters of tumor growth and vehicles for targeted delivery of anticancer agents. World J.Stem Cells 2010; 2:5-12 |
| [7] | Bhattacharya A. Methylselenocysteine: a promising antiangiogenic agent for overcoming drug delivery barriers in solid malignancies for therapeutic synergy with anticancer drugs. Expert.Opin.Drug Deliv. 2011; 8:749-763 |
| [8] | Pascucci L, Cocce V, Bonomi A, Ami D, Ceccarelli P, Ciusani E, Vigano L, Locatelli A, Sisto F, Doglia SM, Parati E, Bernardo ME, Muraca M, Alessandri G, Bondiolotti G, Pessina A. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery. J.Control Release 2014; 192:262-270 |
| [9] | Lim ML, Ooi BN, Jungebluth P, Sjoqvist S, Hultman I, Lemon G, Gustafsson Y, Asmundsson J, Baiguera S, Douagi I, Gilevich I, Popova A, Haag JC, Rodriguez AB, Lim J, Lieden A, Nordenskjold M, Alici E, Baker D, Unger C, Luedde T, Vassiliev I, Inzunza J, Ahrlund-Richter L, Macchiarini P. Characterization of stem-like cells in mucoepidermoid tracheal paediatric tumor. PLoS.One. 2014; 9:e107712 |
| [10] | El-Jawhari JJ, El-Sherbiny YM, Jones EA, McGonagle D. Mesenchymal stem cells, autoimmunity and rheumatoid arthritis. QJM. 2014; 107:505-514 |
| [11] | Eseonu OI, De BC. Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted delivery in arthritis. Rheumatology.(Oxford) 2014; |
| [12] | Soria G, Ben-Baruch A. The inflammatory chemokines CCL2 and CCL5 in breast cancer. Cancer Lett. 2008; 267:271-285 |
| [13] | Nwabo Kamdje AH, Seke Etet PF, Vecchio L, Muller JM, Krampera M, Lukong KE. Signaling pathways in breast cancer: Therapeutic targeting of the microenvironment. Cell Signal. 2014; 26:2843-2856 |
| [14] | Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, Haluska P, Ingle JN, Hartmann LC, Manjili MH, Radisky DC, Ferrone S, Knutson KL. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009; 69:2887-2895 |
| [15] | Payne KK, Manjili MH. Adaptive immune responses associated with breast cancer relapse. Arch.Immunol.Ther.Exp.(Warsz.) 2012; 60:345-350 |
| [16] | Hanson S, D'Souza RN, Hematti P. Biomaterial-mesenchymal stem cell constructs for immunomodulation in composite tissue engineering. Tissue Eng Part A 2014; 20:2162-2168 |
| [17] | Clover AJ, Kumar AH, Isakson M, Whelan D, Stocca A, Gleeson BM, Caplice NM. Allogeneic mesenchymal stem cells, but not culture modified monocytes, improve burn wound healing. Burns 2014; |
| [18] | Linero I, Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS.One. 2014; 9:e107001 |
| [19] | Ozawa K, Sato K, Oh I, Ozaki K, Uchibori R, Obara Y, Kikuchi Y, Ito T, Okada T, Urabe M, Mizukami H, Kume A. Cell and gene therapy using mesenchymal stem cells (MSCs). J.Autoimmun. 2008; 30:121-127 |
| [20] | Seke Etet PF, Nwabo Kamdje AH, Mbo Amvene J, Aldebasi Y, Farahna M, Vecchio L. Stromal control of chronic lymphocytic leukemia cells. Research & Reports in Biology 2013; 4:23-32 |
| [21] | El-Haibi CP, Karnoub AE. Mesenchymal stem cells in the pathogenesis and therapy of breast cancer. J.Mammary.Gland.Biol.Neoplasia. 2010; 15:399-409 |
| [22] | 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; 96:1593-1603 |
| [23] | Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res. 2005; 65:3307-3318 |
| [24] | Komarova S, Kawakami Y, Stoff-Khalili MA, Curiel DT, Pereboeva L. Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses. Mol.Cancer Ther. 2006; 5:755-766 |
| [25] | Klopp AH, Spaeth EL, Dembinski JL, Woodward WA, Munshi A, Meyn RE, Cox JD, Andreeff M, Marini FC. Tumor irradiation increases the recruitment of circulating mesenchymal stem cells into the tumor microenvironment. Cancer Res. 2007; 67:11687-11695 |
| [26] | Menon LG, Picinich S, Koneru R, Gao H, Lin SY, Koneru M, Mayer-Kuckuk P, Glod J, Banerjee D. Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells. Stem Cells 2007; 25:520-528 |
| [27] | Coffelt SB, Marini FC, Watson K, Zwezdaryk KJ, Dembinski JL, LaMarca HL, Tomchuck SL, Honer zu BK, Danka ES, Henkle SL, Scandurro AB. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc.Natl.Acad.Sci.U.S.A 2009; 106:3806-3811 |
| [28] | Duan X, Guan H, Cao Y, Kleinerman ES. Murine bone marrow-derived mesenchymal stem cells as vehicles for interleukin-12 gene delivery into Ewing sarcoma tumors. Cancer 2009; 115:13-22 |
| [29] | Ryu H, Oh JE, Rhee KJ, Baik SK, Kim J, Kang SJ, Sohn JH, Choi E, Shin HC, Kim YM, Kim HS, Bae KS, Eom YW. Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-beta and suppress the growth of MCF-7 human breast cancer cells. Cancer Lett. 2014; 352:220-227 |
| [30] | Zhou Y, Zuo D, Wang M, Zhang Y, Yu M, Yang J, Yao Z. Effect of truncated neurokinin-1 receptor expression changes on the interaction between human breast cancer and bone marrow-derived mesenchymal stem cells. Genes Cells 2014; 19:676-691 |
| [31] | Kucerova L, Skolekova S, Matuskova M, Bohac M, Kozovska Z. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells. BMC.Cancer 2013; 13:535 |
| [32] | Leng L, Wang Y, He N, Wang D, Zhao Q, Feng G, Su W, Xu Y, Han Z, Kong D, Cheng Z, Xiang R, Li Z. Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy. Biomaterials 2014; 35:5162-5170 |
| [33] | Vegh I, Grau M, Gracia M, Grande J, de la Torre P, Flores AI. Decidua mesenchymal stem cells migrated toward mammary tumors in vitro and in vivo affecting tumor growth and tumor development. Cancer Gene Ther. 2013; 20:8-16 |
| [34] | May CD, Sphyris N, Evans KW, Werden SJ, Guo W, Mani SA. Epithelial-mesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression. Breast Cancer Res. 2011; 13:202 |
| [35] | 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:e4992 |
| [36] | El-Haibi CP, Bell GW, Zhang J, Collmann AY, Wood D, Scherber CM, Csizmadia E, Mariani O, Zhu C, Campagne A, Toner M, Bhatia SN, Irimia D, Vincent-Salomon A, Karnoub AE. Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. Proc.Natl.Acad.Sci.U.S.A 2012; 109:17460-17465 |
| [37] | Rappa G, Mercapide J, Lorico A. Spontaneous formation of tumorigenic hybrids between breast cancer and multipotent stromal cells is a source of tumor heterogeneity. Am.J.Pathol. 2012; 180:2504-2515 |
| [38] | Jain P, Alahari SK. Breast cancer stem cells: a new challenge for breast cancer treatment. Front Biosci.(Landmark.Ed) 2011; 16:1824-1832 |
| [39] | Ito Y, Iwase T, Hatake K. Eradication of breast cancer cells in patients with distant metastasis: the finishing touches? Breast Cancer 2012; 19:206-211 |
| [40] | Yu Y, Ramena G, Elble RC. The role of cancer stem cells in relapse of solid tumors. Front Biosci.(Elite.Ed) 2012; 4:1528-1541 |
| [41] | Malik B, Nie D. Cancer stem cells and resistance to chemo and radio therapy. Front Biosci.(Elite.Ed) 2012; 4:2142-2149 |
| [42] | Biddle A, Gammon L, Fazil B, Mackenzie IC. CD44 staining of cancer stem-like cells is influenced by down-regulation of CD44 variant isoforms and up-regulation of the standard CD44 isoform in the population of cells that have undergone epithelial-to-mesenchymal transition. PLoS.One. 2013; 8:e57314 |
| [43] | Feng YX, Sokol ES, Del Vecchio CA, Sanduja S, Claessen JH, Proia TA, Jin DX, Reinhardt F, Ploegh HL, Wang Q, Gupta PB. Epithelial-to-mesenchymal transition activates PERK-eIF2alpha and sensitizes cells to endoplasmic reticulum stress. Cancer Discov. 2014; 4:702-715 |
| [44] | Guo W. Concise review: breast cancer stem cells: regulatory networks, stem cell niches, and disease relevance. Stem Cells Transl.Med. 2014; 3:942-948 |
| [45] | Ferrand N, Gnanapragasam A, Dorothee G, Redeuilh G, Larsen AK, Sabbah M. Loss of WISP2/CCN5 in estrogen-dependent MCF7 human breast cancer cells promotes a stem-like cell phenotype. PLoS.One. 2014; 9:e87878 |
| [46] | Shi J, Wang Y, Zeng L, Wu Y, Deng J, Zhang Q, Lin Y, Li J, Kang T, Tao M, Rusinova E, Zhang G, Wang C, Zhu H, Yao J, Zeng YX, Evers BM, Zhou MM, Zhou BP. Disrupting the interaction of BRD4 with diacetylated Twist suppresses tumorigenesis in basal-like breast cancer. Cancer Cell 2014; 25:210-225 |
| [47] | Wang KH, Kao AP, Chang CC, Lin TC, Kuo TC. Bisphenol A at environmentally relevant doses induces cyclooxygenase-2 expression and promotes invasion of human mesenchymal stem cells derived from uterine myoma tissue. Taiwan.J.Obstet.Gynecol. 2013; 52:246-252 |
| [48] | Rameshwar P. Would cancer stem cells affect the future investment in stem cell therapy. World J.Exp.Med. 2012; 2:26-29 |
| [49] | Austin J, Kimble J. glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell 1987; 51:589-599 |
| [50] | Henrique D, Hirsinger E, Adam J, Le R, I, Pourquie O, Ish-Horowicz D, Lewis J. Maintenance of neuroepithelial progenitor cells by Delta-Notch signalling in the embryonic chick retina. Curr.Biol. 1997; 7:661-670 |
| [51] | Chan EF, Gat U, McNiff JM, Fuchs E. A common human skin tumour is caused by activating mutations in beta-catenin. Nat.Genet. 1999; 21:410-413 |
| [52] | Wechsler-Reya RJ, Scott MP. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 1999; 22:103-114 |
| [53] | Zhu AJ, Watt FM. beta-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development 1999; 126:2285-2298 |
| [54] | Polakis P. Wnt signaling and cancer. Genes Dev. 2000; 14:1837-1851 |
| [55] | Zhang Y, Kalderon D. Hedgehog acts as a somatic stem cell factor in the Drosophila ovary. Nature 2001; 410:599-604 |
| [56] | Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc.Natl.Acad.Sci.U.S.A 2003; 100:3983-3988 |
| [57] | Chirgwin JM. The stem cell niche as a pharmaceutical target for prevention of skeletal metastases. Anticancer Agents Med.Chem. 2012; 12:187-193 |
| [58] | Arend RC, Londono-Joshi AI, Straughn JM, Jr., Buchsbaum DJ. The Wnt/beta-catenin pathway in ovarian cancer: a review. Gynecol.Oncol. 2013; 131:772-779 |
| [59] | Gonzalez DM, Medici D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci.Signal. 2014; 7:re8 |
| [60] | Klauzinska M, Castro NP, Rangel MC, Spike BT, Gray PC, Bertolette D, Cuttitta F, Salomon D. The multifaceted role of the embryonic gene Cripto-1 in cancer, stem cells and epithelial-mesenchymal transition. Semin.Cancer Biol. 2014; |
| [61] | Fazilaty H, Mehdipour P. Genetics of breast cancer bone metastasis: a sequential multistep pattern. Clin.Exp.Metastasis 2014; 31:595-612 |
| [62] | Deonarain MP, Kousparou CA, Epenetos AA. Antibodies targeting cancer stem cells: a new paradigm in immunotherapy? MAbs. 2009; 1:12-25 |
| [63] | Zimmerlin L, Park TS, Zambidis ET, Donnenberg VS, Donnenberg AD. Mesenchymal stem cell secretome and regenerative therapy after cancer. Biochimie 2013; 95:2235-2245 |
| [64] | Chung SS, Giehl N, Wu Y, Vadgama JV. STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits. Int.J.Oncol. 2014; 44:403-411 |
| [65] | 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; 4:70 |
| [66] | Kuo CH, Liu CJ, Lu CY, Hu HM, Kuo FC, Liou YS, Yang YC, Hsieh MC, Lee OK, Wu DC, Wang SS, Chen YL. 17beta-estradiol inhibits mesenchymal stem cells-induced human AGS gastric cancer cell mobility via suppression of. Int.J.Med.Sci. 2014; 11:7-16 |
| [67] | Orciani M, Lazzarini R, Scartozzi M, Bolletta E, Mattioli-Belmonte M, Scalise A, Di BG, Di PR. The response of breast cancer cells to mesenchymal stem cells: a possible role of inflammation by breast implants. Plast.Reconstr.Surg. 2013; 132:899e-910e |
| [68] | Pearl RA, Leedham SJ, Pacifico MD. The safety of autologous fat transfer in breast cancer: lessons from stem cell biology. J.Plast.Reconstr.Aesthet.Surg. 2012; 65:283-288 |
| [69] | Smalley M, Piggott L, Clarkson R. Breast cancer stem cells: obstacles to therapy. Cancer Lett. 2013; 338:57-62 |
| [70] | Krumboeck A, Giovanoli P, Plock JA. Fat grafting and stem cell enhanced fat grafting to the breast under oncological aspects--recommendations for patient selection. Breast 2013; 22:579-584 |
| [71] | Bibber B, Sinha G, Lobba AR, Greco SJ, Rameshwar P. A review of stem cell translation and potential confounds by cancer stem cells. Stem Cells Int. 2013; 2013:241048 |
| [72] | Lin JJ, Huang CS, Yu J, Liao GS, Lien HC, Hung JT, Lin RJ, Chou FP, Yeh KT, Yu AL. Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells. Breast Cancer Res. 2014; 16:R29 |
| [73] | Ke CC, Liu RS, Suetsugu A, Kimura H, Ho JH, Lee OK, Hoffman RM. In vivo fluorescence imaging reveals the promotion of mammary tumorigenesis by mesenchymal stromal cells. PLoS.One. 2013; 8:e69658 |
| [74] | Shangguan L, Ti X, Krause U, Hai B, Zhao Y, Yang Z, Liu F. Inhibition of TGF-beta/Smad signaling by BAMBI blocks differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and abolishes their protumor effects. Stem Cells 2012; 30:2810-2819 |
| [75] | Lee RH, Yoon N, Reneau JC, Prockop DJ. Preactivation of human MSCs with TNF-alpha enhances tumor-suppressive activity. Cell Stem Cell 2012; 11:825-835 |
APA Style
Armel Herve Nwabo Kamdje, Paul Faustin Seke Etet, Kiven Erique Lukong. (2015). Mesenchymal Stem Cell Therapy for Breast Cancer: Challenges Remaining. International Journal of Biomedical Science and Engineering, 2(6-1), 20-24. https://doi.org/10.11648/j.ijbse.s.2014020601.13
ACS Style
Armel Herve Nwabo Kamdje; Paul Faustin Seke Etet; Kiven Erique Lukong. Mesenchymal Stem Cell Therapy for Breast Cancer: Challenges Remaining. Int. J. Biomed. Sci. Eng. 2015, 2(6-1), 20-24. doi: 10.11648/j.ijbse.s.2014020601.13
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.ijbse.s.2014020601.13,
author = {Armel Herve Nwabo Kamdje and Paul Faustin Seke Etet and Kiven Erique Lukong},
title = {Mesenchymal Stem Cell Therapy for Breast Cancer: Challenges Remaining},
journal = {International Journal of Biomedical Science and Engineering},
volume = {2},
number = {6-1},
pages = {20-24},
doi = {10.11648/j.ijbse.s.2014020601.13},
url = {https://doi.org/10.11648/j.ijbse.s.2014020601.13},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijbse.s.2014020601.13},
abstract = {The treatment of breast cancer, the most common malignancy among women worldwide, remains puzzling partly due to the resistance to therapeutics, which associates with the heterogeneity of case clinical presentations, and limits in the current understanding of the pathogenesis of solid cancers. Notably, it remains unclear: (i) whether breast cancer starts strictly as a local disease before metastasizing to the lymph nodes and distant organs, i.e. if cancer initiating cells are local cells that have undergone epithelial to mesenchymal transition; (ii) or if breast cancer is intrinsically a systemic disease started by malfunctioning circulating mesenchymal stem cells (MSCs) infiltrating the breast stroma to start tumorigenesis. Such limits in our understanding of breast cancer biology have been slowing the development of MSC-based therapies exploiting the ability of these cells to home into tumorigenic sites, kill cancer cells, stop neoangiogenesis, and repair damaged tissues, as well as therapeutic approaches using these cells as vehicle for gene therapy and for delivering anticancer therapeutics, which are potential game changing therapeutic approaches, particularly in currently incurable cancers and intractable cases. Major drawbacks to MSC-based therapy implementation and use in breast cancer are herein briefly discussed.},
year = {2015}
}
TY - JOUR T1 - Mesenchymal Stem Cell Therapy for Breast Cancer: Challenges Remaining AU - Armel Herve Nwabo Kamdje AU - Paul Faustin Seke Etet AU - Kiven Erique Lukong Y1 - 2015/01/27 PY - 2015 N1 - https://doi.org/10.11648/j.ijbse.s.2014020601.13 DO - 10.11648/j.ijbse.s.2014020601.13 T2 - International Journal of Biomedical Science and Engineering JF - International Journal of Biomedical Science and Engineering JO - International Journal of Biomedical Science and Engineering SP - 20 EP - 24 PB - Science Publishing Group SN - 2376-7235 UR - https://doi.org/10.11648/j.ijbse.s.2014020601.13 AB - The treatment of breast cancer, the most common malignancy among women worldwide, remains puzzling partly due to the resistance to therapeutics, which associates with the heterogeneity of case clinical presentations, and limits in the current understanding of the pathogenesis of solid cancers. Notably, it remains unclear: (i) whether breast cancer starts strictly as a local disease before metastasizing to the lymph nodes and distant organs, i.e. if cancer initiating cells are local cells that have undergone epithelial to mesenchymal transition; (ii) or if breast cancer is intrinsically a systemic disease started by malfunctioning circulating mesenchymal stem cells (MSCs) infiltrating the breast stroma to start tumorigenesis. Such limits in our understanding of breast cancer biology have been slowing the development of MSC-based therapies exploiting the ability of these cells to home into tumorigenic sites, kill cancer cells, stop neoangiogenesis, and repair damaged tissues, as well as therapeutic approaches using these cells as vehicle for gene therapy and for delivering anticancer therapeutics, which are potential game changing therapeutic approaches, particularly in currently incurable cancers and intractable cases. Major drawbacks to MSC-based therapy implementation and use in breast cancer are herein briefly discussed. VL - 2 IS - 6-1 ER -
Email: