Behaviour of mesenchymal stem cells from bone marrow of untreated advanced breast and lung cancer patients before bone osteolytic metastasis

Authors
Fernández Vallone, Valeria Beatriz; Hofer, Erica L.; Choi, Hosoon; Bordenave, Raúl H.; Batagelj, Emilio; Feldman, Leonardo; La Russa, Vincent; Caramutti, Daniela; Dimase, Federico; Labovsky, Vivian; Martinez, Leandro Marcelo; Chasseing, Norma Alejandra
Publication Year
2013
Language
English
Format
article
Status
Published version
Description
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.
Fil: Fernández Vallone, Valeria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Hofer, Erica L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Choi, Hosoon. Texas A&M Health Science Center; Estados Unidos
Fil: Bordenave, Raúl H.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos "Dr. Isidoro G. Iriarte" Quilmes; Argentina
Fil: Batagelj, Emilio. Ministerio de Defensa. Ejercito Argentino. Hospital Militar Central Cirujano Mayor "Cosme Argerich"; Argentina
Fil: Feldman, Leonardo. Fundacion Favaloro; Argentina
Fil: La Russa, Vincent. Memorial Sloan Kettering Cancer Center; Estados Unidos
Fil: Caramutti, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Dimase, Federico. Ministerio de Defensa. Ejercito Argentino. Hospital Militar Central Cirujano Mayor "Cosme Argerich"; Argentina
Fil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Martinez, Leandro Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Subject
CELULAS MADRE MESENQUIMALES
OSTEOGENESIS
CANCER DE MAMA
METASTASIS OSEA
MEDICINA REGENERATIVA
BONE MARROW
Medicina Química
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Oncología
Medicina Clínica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/5777