Skip to main content
Log in

Marrow-derived mesenchymal stem cells: Role in epithelial tumor cell determination

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Marrow stroma represents an advantageous environment for development of micrometastatic cells. Within the cellular structure of marrow stroma, mesenchymal stem cells (MSC) have been postulated as an interacting target for disseminated cancer cells. The studies reported here were performed to gain more information on the interaction of the human breast cancer cell line MCF-7 with human bone marrow-derived MSC cells and to investigate whether this interaction affects tumor cell properties. The results showed that after co-culture with MSC, changes were detected in the morphology, proliferative capacity and aggregation pattern of MCF-7 cells, but these parameters were not affected after the co-culture of MSC cells with a non-tumorigenic breast epithelial cell line, MCF-10. Since the indirect culture of MCF-7 with MSC or its products also resulted in functional changes in the tumor cells, we evaluated whether these effects could be attributed to growth factors produced by MSC cells. It was found that VEGF and IL-6 mimic the effects produced by MSC or its products on the proliferation and aggregation properties of MCF-7, cells, respectively. Thus, it seems that after entry of disseminated tumor cells into the marrow space, their proliferative and morphogenetic organization patterns are modified after interaction with distinct stromal cells and/or with specific signals from the marrow microenvironment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lapidot T, Petit I. understanding of stem cell mobilization: The roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 2002; 30: 973–81.

    Article  PubMed  CAS  Google Scholar 

  2. Pittenger M, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–7.

    Article  PubMed  CAS  Google Scholar 

  3. Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med 2001; 226: 507–20.

    CAS  Google Scholar 

  4. Levesque JP, Haylock DN, Simmons PJ. Cytokine regulation of proliferation and cell adhesion are correlated events in human CD34 +hemopoietic progenitors. Blood 1996; 88: 1168–76.

    PubMed  CAS  Google Scholar 

  5. Wiedswang G, Borgen E, Karesen R et al. Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 2003; 21: 3469–78.

    Article  PubMed  CAS  Google Scholar 

  6. Pantel K, Muller V, Auer M et al. Detection and clinical implications of early systemic tumor cell dissemination in breast cancer. Clin Cancer Res 2003; 9: 6326–34.

    PubMed  CAS  Google Scholar 

  7. Brooks B, Bundred NJ, Howell A et al. Investigation of mammary epithelial cell-bone marrow stroma interactions using primary human cell culture as a model of metastasis. Int J Cancer 1997; 73: 690–6.

    Article  PubMed  CAS  Google Scholar 

  8. Hombauer H, Minguell JJ. Selective interactions between epithelial tumor cells and bone marrow mesenchymal stem cells. Br J Cancer 2000; 82: 1290–6.

    Article  PubMed  CAS  Google Scholar 

  9. Nicola MH, Bizon R, Machado JJ et al. Breast cancer micrometa-stases: different interactions of carcinoma cells with normal and cancer patients' bone marrow stromata. Clin Exp Metast 2003; 20: 471–9.

    Article  Google Scholar 

  10. Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 1999; 81: 67–73.

    Article  Google Scholar 

  11. Conget PA, Allers C, Minguell JJ. Identification of a discrete population of human bone-marrow derived mesenchymal cells exhibiting properties of uncommitted progenitors. J Hematother Stem Cell Res 2001; 10: 749–58.

    Article  PubMed  CAS  Google Scholar 

  12. Benavente CA, Sierralta WD, Conget PA, Minguell JJ. Subcellular distribution and mitogenic effect of basic fibroblast growth factor in mesenchymal uncommitted stem cells. Growth Factors 2003; 21: 87–94.

    Article  PubMed  CAS  Google Scholar 

  13. Sierralta WD. Immunoelectron microscopy in embryos. Methods 2001; 24: 61–9.

    Article  PubMed  CAS  Google Scholar 

  14. Erices A, Conget P, Rojas C, Minguell JJ. Gp130 activation by soluble interleukin-6 receptor/interleukin-6 enhances osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. Exp Cell Res 2002; 280: 24–32.

    Article  PubMed  CAS  Google Scholar 

  15. Bischoff J, Rosenberg R, Dahm M et al. Minimal residual disease in bone marrow and peripheral blood of patients with metastatic breast cancer. Rec Res Cancer Res 2003; 162: 35–140.

    Google Scholar 

  16. Pierga JY, Bonneton C, Magdelenat H et al. Clinical significance of proliferative potential of occult metastatic cells in bone marrow of patients with breast cancer. Br J Cancer 2003; 89: 539–45.

    Article  PubMed  Google Scholar 

  17. Maguire D, O'Sullivan GC, Collins JK et al. Bone marrow micro-metastases and gastrointestinal cancer detection and significance. Am J Gastroenterol 2000; 95: 1644–51.

    Article  PubMed  CAS  Google Scholar 

  18. Hazan RB, Kang L, Whooley BP, Borgen PI. N-cadherin promotes adhesion between invasive breast cancer cells and the stroma. Cell Adhes Commun 1997; 4: 399–411.

    PubMed  CAS  Google Scholar 

  19. Shekhar MP, Pauley R, Heppner G. Host microenvironment in breast cancer development: Extracellular matrix-stromal cell contribution to neoplastic phenotype of epithelial cells in the breast. Breast Cancer Res 2003; 5: 130–5.

    Article  PubMed  CAS  Google Scholar 

  20. Motta PM, Nottola SA, Makabe S, Heyn R. Mitochondrial morphology in human fetal and adult female germ cells. Hum Reprod 2000; 15 (Suppl 2): 129–47.

    PubMed  Google Scholar 

  21. Majumdar MK, Thiede MA, Mosca JD et al. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 1998; 176: 57–66.

    Article  PubMed  CAS  Google Scholar 

  22. Asgeirsson KS, Olafsdottir K, Jonasson JG, Ogmundsdottir HM. The effects of IL-6 on cell adhesion and ecadherin expression in breast cancer. Cytokine 1998; 10: 720–8.

    Article  PubMed  CAS  Google Scholar 

  23. McLeskey SW, Tobias CA, Vezza PR et al. Tumor growth of FGF or VEGF transfected MCF-7 breast carcinoma cells correlates with density of specific microvessels independent of the transfected angiogenic factor. Am J Pathol 1998; 153: 1993–2006.

    PubMed  CAS  Google Scholar 

  24. Funke I, Fries S, Rolle M et al. Comparative analyses of bone marrow micrometastases in breast and gastric cancer. Int J Cancer 1996; 65: 755–61.

    Article  PubMed  CAS  Google Scholar 

  25. Borgen E, Naume B, Nesland JM et al. Standardisation of the immunocyochemical detection of cancer cells in bone marrow and blood: 1. Establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy 1999; 5: 377–88.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José J. Minguell.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fierro, F.A., Sierralta, W.D., Epuñan, M.J. et al. Marrow-derived mesenchymal stem cells: Role in epithelial tumor cell determination. Clin Exp Metastasis 21, 313–319 (2004). https://doi.org/10.1023/B:CLIN.0000046130.79363.33

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:CLIN.0000046130.79363.33

Navigation