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Cited by 92Mesenchymal stem cell researchCancer Cells and MetastasisExtracellular vesicles in disease

Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells

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Eiró, Noemí, Sendon-Lago, Juan, Seoane, Samuel, Bermúdez, María A., Lamelas, Maria Luz, Garcia-Caballero, Tomás, Schneider, José, Perez-Fernandez, Roman +1 more·2014·Oncotarget
DOI 10.18632/oncotarget.2530PMC PMC4279403
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Abstract

// Noemí Eiró 1,5,* , Juan Sendon-Lago 2,* , Samuel Seoane 2 , María A. Bermúdez 2 , Maria Luz Lamelas 1 , Tomás Garcia-Caballero 3 , José Schneider 4,5 , Roman Perez-Fernandez 2,5 and Francisco J. Vizoso 1,5 1 Unidad de Investigación, Fundación Hospital de Jove, Gijón, Spain 2 Departamento de Fisiología-CIMUS, Universidad de Santiago de Compostela, Spain 3 Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela, Spain 4 Universidad Rey Juan Carlos, Facultad de Ciencias de la Salud, Spain 5 Fundación para la Investigación con Células Madre Uterinas (FICEMU), Gijón, Spain * These authors contributed equally to this work Correspondence: Francisco J. Vizoso, email: // Keywords : Mesenchymal stem cell; uterine cervix; breast cancer; tumor stroma; cancer-associated fibroblasts; macrophages Received : July 16, 2014 Accepted : September 25, 2014 Published : September 26, 2014 Abstract Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancer cells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancer cells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy.

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Research works printed but not linked: 55

  1. [1]Marsh T Pietras K McAllister SS Fibroblasts as architects of cancer pathogenesis Biochim Biophys Acta 2013 1832 1070 1078 23123598 PMC3775582
  2. [2]Finak G Bertos N Pepin F Sadekova S Souleimanova M Zhao H Chen H Omeroglu G Meterissian S Omeroglu A Hallett M Park M Stromal gene expression predicts clinical outcome in breast cancer Nat Med 2008 14 518 527 18438415
  3. [3]Sloan EK Ciocca DR Pouliot N Natoli A Restall C Henderson MA Fanelli MA Cuello-Carrion FD Gago FE Anderson RL Stromal cell expression of caveolin-1 predicts outcome in breast cancer Am J Pathol 2009 174 2035 2043 19411449 PMC2684169
  4. [4]Farmer P Bonnefoi H Anderle P Cameron D Wirapati P Becette V Andre S Piccart M Campone M Brain E Macgrogan G Petit T Jassem J A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer Nat Med 2009 15 68 74 19122658
  5. [5]Ahn S Cho J Sung J Lee JE Nam SJ Kim KM Cho EY The prognostic significance of tumor-associated stroma in invasive breast carcinoma Tumour Biol 2012 33 1573 1580 22581521
  6. [6]Mao Y Keller ET Garfield DH Shen K Wang J Stromal cells in tumor microenvironment and breast cancer Cancer Metastasis Rev 2013 32 303 315 23114846 PMC4432936
  7. [7]Allavena P Sica A Solinas G Porta C Mantovani A The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages Crit Rev Oncol Hematol 2008 66 1 9 17913510
  8. [8]Solinas G Schiarea S Liguori M Fabbri M Pesce S Zammataro L Pasqualini F Nebuloni M Chiabrando C Mantovani A Allavena P Tumor-conditioned macrophages secrete migration-stimulating factor: a new marker for M2-polarization, influencing tumor cell motility J Immunol 2010 185 642 652 20530259
  9. [9]Singer NG Caplan AI Mesenchymal stem cells: mechanisms of inflammation Annu Rev Pathol 2011 6 457 478 21073342
  10. [10]Uccelli A Moretta L Pistoia V Mesenchymal stem cells in health and disease Nat Rev Immunol 2008 8 726 736 19172693
  11. [11]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 284 143 147 10102814
  12. [12]Colter DC Class R DiGirolamo CM Prockop DJ Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow Proc Natl Acad Sci U S A 2000 97 3213 3218 10725391 PMC16218
  13. [13]Zuk PA Zhu M Ashjian P De Ugarte DA Huang JI Mizuno H Alfonso ZC Fraser JK Benhaim P Hedrick MH Human adipose tissue is a source of multipotent stem cells Mol Biol Cell 2002 13 4279 4295 12475952 PMC138633
  14. [14]Bieback K Kluter H Mesenchymal stromal cells from umbilical cord blood Curr Stem Cell Res Ther 2007 2 310 323 18220915
  15. [15]Fukuchi Y Nakajima H Sugiyama D Hirose I Kitamura T Tsuji K Human placenta-derived cells have mesenchymal stem/progenitor cell potential Stem Cells 2004 22 649 658 15342929
  16. [16]Hida N Nishiyama N Miyoshi S Kira S Segawa K Uyama T Mori T Miyado K Ikegami Y Cui C Kiyono T Kyo S Shimizu T Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells Stem Cells 2008 26 1695 1704 18420831
  17. [17]Meng X Ichim TE Zhong J Rogers A Yin Z Jackson J Wang H Ge W Bogin V Chan KW Thebaud B Riordan NH Endometrial regenerative cells: a novel stem cell population J Transl Med 2007 5 57 66 18005405 PMC2212625
  18. [18]Galvez BG Martin NS Salama-Cohen P Lazcano JJ Coronado MJ Lamelas ML Alvarez-Barrientes A Eiro N Vizoso F Rodriguez C An adult myometrial pluripotential precursor that promotes healing of damaged muscular tissues In Vivo 2010 24 431 441 20668309
  19. [19]Ono M Maruyama T Masuda H Kajitani T Nagashima T Arase T Ito M Ohta K Uchida H Asada H Yoshimura Y Okano H Matsuzaki Y Side population in human uterine myometrium displays phenotypic and functional characteristics of myometrial stem cells Proc Natl Acad Sci U S A 2007 104 18700 18705 18003928 PMC2141840
  20. [20]Montesinos JJ Mora-Garcia Mde L Mayani H Flores-Figueroa E Garcia-Rocha R Fajardo-Orduna GR Castro-Manrreza ME Weiss-Steider B Monroy-Garcia A evidence of the presence of mesenchymal stromal cells in cervical cancer and their role in protecting cancer cells from cytotoxic T cell activity Stem Cells Dev 2013 22 2508 2519 23656504 PMC3761677
  21. [21]Ribeiro A Laranjeira P Mendes S Velada I Leite C Andrade P Santos F Henriques A Graos M Cardoso CM Martinho A Pais M da Silva CL Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells Stem Cell Res Ther 2013 4 125 140 24406104 PMC3854702
  22. [22]Akimoto K Kimura K Nagano M Takano S To'a Salazar G Yamashita T Ohneda O Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote, glioblastoma multiforme proliferation Stem Cells Dev 2013 22 1370 1386 23231075 PMC3696928
  23. [24]Dominici M Le Blanc K Mueller I Slaper-Cortenbach I Marini F Krause D Deans R Keating A Prockop D Horwitz E Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement Cytotherapy 2006 8 315 317 16923606
  24. [25]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 449 557 563 17914389
  25. [27]Galie M Konstantinidou G Peroni D Scambi I Marchini C Lisi V Krampera M Magnani P Merigo F Montani M Boschi F Marzola P Orru R Mesenchymal stem cells share molecular signature with mesenchymal tumor cells and favor early tumor growth in syngeneic mice Oncogene 2008 27 2542 2551 17998939
  26. [28]Bhowmick NA Neilson EG Moses HL Stromal fibroblasts in cancer initiation and progression Nature 2004 432 332 337 15549095 PMC3050735
  27. [29]Vizoso FJ Gonzalez LO Corte MD Rodriguez JC Vazquez J Lamelas ML Junquera S Merino AM Garcia-Muniz JL Study of matrix metalloproteinases and their inhibitors in breast cancer Br J Cancer 2007 96 903 911 17342087 PMC2360108
  28. [30]Del Casar JM Gonzalez LO Alvarez E Junquera S Marin L Gonzalez L Bongera M Vazquez J Vizoso FJ Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas Breast Cancer Res Treat 2009 116 39 52 19241156
  29. [31]Kalluri R Zeisberg M Fibroblasts in cancer Nat Rev Cancer 2006 6 392 401 16572188
  30. [32]Mao Y Keller ET Garfield DH Shen K Wang J Stromal cells in tumor microenvironment and breast cancer Cancer Metastasis Rev 2013 32 303 315 23114846 PMC4432936
  31. [33]Becker JC Andersen MH Schrama D Thor Straten P Immune-suppressive properties of the tumor microenvironment Cancer Immunol Immunother 2013 62 1137 1148 23666510 PMC11029603
  32. [34]Zhang QW Liu L Gong CY Shi HS Zeng YH Wang XZ Zhao YW Wei YQ Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature PLoS One 2012 7 e50946 23284651 PMC3532403
  33. [35]Mukhtar RA Nseyo O Campbell MJ Esserman LJ Tumor-associated macrophages in breast cancer as potential biomarkers for new treatments and diagnostics Expert Rev Mol Diagn 2011 11 91 100 21171924
  34. [36]Eiro N Pidal I Fernandez-Garcia B Junquera S Lamelas ML del Casar JM Gonzalez LO Lopez-Muniz A Vizoso FJ Impact of CD68/(CD3+CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer PLoS One 2012 7 e52796 23300781 PMC3530508
  35. [37]Pasero C Barbarat B Just-Landi S Bernard A Aurran-Schleinitz T Rey J Eldering E Truneh A Costello RT Olive D A role for HVEM, but not lymphotoxin-beta receptor, in LIGHT-induced tumor cell death and chemokine production Eur J Immunol 2009 39 2502 2514 19701890
  36. [38]Silver DF Hempling RE Piver MS Repasky EA Flt-3 ligand inhibits growth of human ovarian tumors engrafted in severe combined immunodeficient mice Gynecol Oncol 2000 77 377 382 10831345
  37. [39]Bronger H Kraeft S Schwarz-Boeger U Cerny C Stockel A Avril S Kiechle M Schmitt M Modulation of CXCR3 ligand secretion by prostaglandin E2 and cyclooxygenase inhibitors in human breast cancer Breast Cancer Res 2012 14 R30 22333315 PMC3496148
  38. [40]Bekisz J Sato Y Johnson C Husain SR Puri RK Zoon KC Immunomodulatory effects of interferons in malignancies J Interferon Cytokine Res 2013 33 154 161 23570381 PMC3647483
  39. [41]Tager AM Kradin RL LaCamera P Bercury SD Campanella GS Leary CP Polosukhin V Zhao LH Sakamoto H Blackwell TS Luster AD Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10 Am J Respir Cell Mol Biol 2004 31 395 404 15205180
  40. [42]Annes JP Munger JS Rifkin DB Making sense of latent TGFbeta activation J Cell Sci 2003 116 217 224 12482908
  41. [43]Masuda H Zhang D Bartholomeusz C Doihara H Hortobagyi GN Ueno NT Role of epidermal growth factor receptor in breast cancer Breast Cancer Res Treat 2012 136 331 345 23073759 PMC3832208
  42. [44]Shirakihara T Horiguchi K Miyazawa K Ehata S Shibata T Morita I Miyazono K Saitoh M TGF-beta regulates isoform switching of FGF receptors and epithelial-mesenchymal transition EMBO J 2011 30 783 795 21224849 PMC3041949
  43. [45]Korkaya H Liu S Wicha MS Breast cancer stem cells, cytokine networks, and the tumor microenvironment J Clin Invest 2011 121 3804 3809 21965337 PMC3223613
  44. [46]Park JK Park SH So K Bae IH Yoo YD Um HD ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB Int J Oncol 2010 36 181 192 19956847
  45. [47]Dethlefsen C Hojfeldt G Hojman P The role of intratumoral and systemic IL-6 in breast cancer Breast Cancer Res Treat 2013 138 657 664 23532539
  46. [48]Won HS Kim YA Lee JS Jeon EK An HJ Sun DS Ko YH Kim JS Soluble interleukin-6 receptor is a prognostic marker for relapse-free survival in estrogen receptor-positive breast cancer Cancer Invest 2013 31 516 521 23902164
  47. [49]Rajaram M Li J Egeblad M Powers RS System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity PLoS Genet 2013 9 e1003789 24068959 PMC3778011
  48. [50]Verjans E Noetzel E Bektas N Schutz AK Lue H Lennartz B Hartmann A Dahl E Bernhagen J Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer BMC Cancer 2009 9 230 247 19602265 PMC2716369
  49. [51]Karnezis T Shayan R Caesar C Roufail S Harris NC Ardipradja K Zhang YF Williams SP Farnsworth RH Chai MG Rupasinghe TW Tull DL Baldwin ME VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium Cancer Cell 2012 21 181 195 22340592
  50. [52]McNairn AJ Guasch G Epithelial transition zones: merging microenvironments, niches, and cellular transformation Eur J Dermatol 2011 21 Suppl 2 21 28 21628126
  51. [53]Grizzle WE Srivastava S Manne U The biology of incipient, pre-invasive or intraepithelial neoplasia Cancer Biomark 2010 9 21 39 22112468 PMC3430522
  52. [54]Lucey BP Nelson-Rees WA Hutchins GM Henrietta Lacks, HeLa cells, and cell culture contamination Arch Pathol Lab Med 2009 133 1463 1467 19722756
  53. [55]Seoane S Montero JC Ocana A Pandiella A Effect of multikinase inhibitors on caspase-independent cell death and DNA damage in HER2-overexpressing breast cancer cells J Natl Cancer Inst 2010 102 1432 1446 20811002
  54. [56]Seoane S Diaz-Rodriguez P Sendon-Lago J Gallego R Perez-Fernandez R Landin M Administration of the optimized beta-Lapachone-poloxamer-cyclodextrin ternary system induces apoptosis, DNA damage and reduces tumor growth in a human breast adenocarcinoma xenograft mouse model Eur J Pharm Biopharm 2013 84 497 504 23333901
  55. [57]Ben-Batalla I Seoane S Garcia-Caballero T Gallego R Macia M Gonzalez LO Vizoso F Perez-Fernandez R Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis J Clin Invest 2010 120 4289 4302 21060149 PMC2993584

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Authors
Eiró, N., Sendon-Lago, J., Seoane, S., Bermúdez, M. A., Lamelas, M. L., Garcia-Caballero, T., Schneider, J., Perez-Fernandez, R., & Vizoso, F. J.
Affiliations
  • Fundación Hospital de Jove (ES)
  • Departamento de Fisiología-CIMUS, Universidad de Santiago de Compostela, Spain
  • Universidade de Santiago de Compostela (ES)
  • Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela, Spain
  • Universidad Rey Juan Carlos (ES)
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2014-09-26
Volume
5
Issue
21
Pages
10692-10708
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.2530
PMC
PMC4279403
OpenAlex
W1599799946
Cited by
92
References
2
Citations by year
2026: 5 · 2025: 3 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 14 · 2020: 11 · 2019: 13 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 2
FWCI
1.17
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Ministerio de Economía y Competitividad (SAF2012-38240, SAF2012)
  • Instituto de Salud Carlos III (PI13/02745)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
mesenchymal stem cells, secretome, conditioned medium, breast cancer, tumor stroma, cancer-associated fibroblasts, macrophage differentiation, tumor microenvironment, paracrine signaling, adipose-derived stem cells, MDA-MB-231 cells, tumor growth inhibition, apoptosis, cell proliferation, tumor invasion, xenografts
MeSH terms
Adipose Tissue, Animals, Breast Neoplasms, Cell Cycle, Cell Movement, Cells, Cultured, Cervix Uteri, Female, Flow Cytometry, Humans, Immunoenzyme Techniques, Macrophages, Stem Cells, Blotting, Western, Mice, SCID, Culture Media, Conditioned, Stromal Cells, Apoptosis, Proteome, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Mesenchymal Stem Cells

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