Behaviour of mesenchymal stem cells from bone marrow of untreated advanced breast and lung cancer patients without bone osteolytic metastasis Journal Article


Authors: Fernández Vallone, V. B.; Hofer, E. L.; Choi, H.; Bordenave, R. H.; Batagelj, E.; Feldman, L.; La Russa, V.; Caramutti, D.; Dimase, F.; Labovsky, V.; Martinez, L. M.; Chasseing, N. A.
Article Title: Behaviour of mesenchymal stem cells from bone marrow of untreated advanced breast and lung cancer patients without bone osteolytic metastasis
Abstract: Tumour cells can find in bone marrow (BM) a niche rich in growth factors and cytokines that promote their self-renewal, proliferation and survival. In turn, tumour cells affect the homeostasis of the BM and bone, as well as the balance among haematopoiesis, osteogenesis, osteoclastogenesis and bone-resorption. As a result, growth and survival factors normally sequestered in the bone matrix are released, favouring tumour development. Mesenchymal stem cells (MSCs) from BM can become tumour-associated fibroblasts, have immunosuppressive function, and facilitate metastasis by epithelial-to-mesenchymal transition. Moreover, MSCs generate osteoblasts and osteocytes and regulate osteoclastogenesis. Therefore, MSCs can play an important pro-tumorigenic role in the formation of a microenvironment that promotes BM and bone metastasis. In this study we showed that BM MSCs from untreated advanced breast and lung cancer patients, without bone metastasis, had low osteogenic and adipogenic differentiation capacity compared to that of healthy volunteers. In contrast, chondrogenic differentiation was increased. Moreover, MSCs from patients had lower expression of CD146. Finally, our data showed higher levels of Dkk-1 in peripheral blood plasma from patients compared with healthy volunteers. Because no patient had any bone disorder by the time of the study we propose that the primary tumour altered the plasticity of MSCs. As over 70 % of advanced breast cancer patients and 30-40 % of lung cancer patients will develop osteolytic bone metastasis for which there is no total cure, our findings could possibly be used as predictive tools indicating the first signs of future bone disease. In addition, as the MSCs present in the BM of these patients may not be able to regenerate bone after the tumour cells invasion into BM/bone, it is possible that they promote the cycle between tumour cell growth and bone destruction.
Keywords: bone neoplasms; bone tumor; osteolysis; flow cytometry; metastasis; reverse transcription polymerase chain reaction; bone marrow; lung neoplasms; pathology; breast neoplasms; enzyme linked immunosorbent assay; lung tumor; reverse transcriptase polymerase chain reaction; breast tumor; real time polymerase chain reaction; enzyme-linked immunosorbent assay; real-time polymerase chain reaction; mesenchymal stroma cell; mesenchymal stromal cells
Journal Title: Clinical and Experimental Metastasis
Volume: 30
Issue: 3
ISSN: 0262-0898
Publisher: Springer  
Date Published: 2013-03-01
Start Page: 317
End Page: 332
Language: English
DOI: 10.1007/s10585-012-9539-4
PUBMED: 23053744
PROVIDER: scopus
DOI/URL:
Notes: --- - "Export Date: 21 May 2013" - "Source: Scopus"
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