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Changes in the peripheral blood and bone marrow from untreated advanced breast cancer patients that are associated with the establishment of bone metastases

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Abstract

Bone metastasis is an incurable complication of breast cancer affecting 70–80 % of advanced patients. It is a multistep process that includes tumour cell mobilisation, intravasation, survival in the circulation, extravasation, migration and proliferation in the bone marrow/bone. Although novel findings demonstrate the bone marrow microenvironment significance in bone metastatic progression, a majority of studies have focused on end-stage disease and little is known about how the pre-metastatic niche arises in the bone marrow/bone tissues. We demonstrated a significant increase in patients’ peripheral blood plasma ability to induce transendothelial migration of MCF-7 cells compared with healthy volunteers. Moreover, high RANKL, MIF and OPG levels in patients’ peripheral blood could play a role in the intravasation, angiogenesis, survival and epithelial–mesenchymal transition of circulating tumour cells. Also, we observed a significant increase in patients’ bone marrow plasma capacity to induce transendothelial migration of MDA-MB231 and MCF-7 cells compared with healthy volunteers. Furthermore, patients’ bone marrow mesenchymal stem cells could control the recruitment of tumour cells, modifying the MCF-7 and MDA-MB231 cell migration. In addition, we found a significantly higher MDA-MB231 cell proliferation when we used patients’ bone marrow plasma compared with healthy volunteers. Interestingly, PDGF-AB, ICAM-1 and VCAM-1 levels in patients’ bone marrow were significantly higher than the values of healthy volunteers, suggesting that they could be involved in the cancer cell extravasation, bone resorption and cancer cell proliferation. We believe that these results can reveal new information about what alterations happen in the bone marrow of advanced breast cancer patients before bone colonisation, changes that create optimal soil for the metastatic cascade progression.

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Acknowledgements

We gratefully thank Marcela F. Bolontrade PhD (Laboratory of Molecular and Cellular Therapy, Fundación Instituto Leloir, Buenos Aires, Argentina) for providing HMEC-1 cells. This work was supported by the Grant PIP2011 from the National Council of Scientific and Technical Research (CONICET), Argentina; Grant PICT2006 from the National Agency for Science and Technology, Argentina; Grant 2006–2008, 2009–2011 and 2011–2013 from the Roemmers Foundation, Argentina; and the Institute for Regenerative Medicine, Texas A&M Health Science Center, Temple, Texas, USA.

Ethical standards

All individuals gave consent prior to participating in these studies. The investigations were approved by the IBYME Ethical Committee and performed in accordance with the principles of the Helsinki Declaration.

Disclosure

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Immunohematology Laboratory, Experimental Biology and Medicine Institute (IBYME), National Council of Scientific and Technical Research (CONICET), 2490 Vuelta de Obligado, 1428, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

    Leandro Marcelo Martinez, Valeria Beatriz Fernández Vallone, Vivian Labovsky, Erica Leonor Hofer & Norma Alejandra Chasseing

  2. Texas A&M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott & White, 5701 Airport Road, Module C., Temple, TX, 76502, USA

    Hosoon Choi

  3. Department of Bone Marrow Transplantation, Favaloro Fundation, 443 Solis, 1428, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

    Leonardo Feldman

  4. Department of Oncology, Iriarte Hospital, 770 Alison Bell, 1878, Quilmes, Buenos Aires, Argentina

    Raúl Horacio Bordenave

  5. Department of Oncology, Central Militar Hospital, 726 Luis María Campos, 1426, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

    Emilio Batagelj

  6. Department of Hemotherapy, Central Militar Hospital, 726 Luis María Campos, 1426, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

    Federico Dimase

  7. Department of Diagnosis and Treatment, Central Militar Hospital, 726 Luis María Campos, 1426, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

    Ana Rodriguez Villafañe

Authors
  1. Leandro Marcelo Martinez
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  2. Valeria Beatriz Fernández Vallone
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  3. Vivian Labovsky
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  4. Hosoon Choi
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  5. Erica Leonor Hofer
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  6. Leonardo Feldman
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  7. Raúl Horacio Bordenave
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  8. Emilio Batagelj
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  9. Federico Dimase
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  10. Ana Rodriguez Villafañe
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  11. Norma Alejandra Chasseing
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Corresponding author

Correspondence to Norma Alejandra Chasseing.

Additional information

Leandro Marcelo Martinez and Valeria Beatriz Fernández Vallone have contributed equally to this study.

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Martinez, L.M., Vallone, V.B.F., Labovsky, V. et al. Changes in the peripheral blood and bone marrow from untreated advanced breast cancer patients that are associated with the establishment of bone metastases. Clin Exp Metastasis 31, 213–232 (2014). https://doi.org/10.1007/s10585-013-9622-5

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  • DOI: https://doi.org/10.1007/s10585-013-9622-5

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