Mesenchymal stem cell secretion of chemokines during differentiation into osteoblasts, and their potential role in mediating interactions with breast cancer cells

Over 70% of patients with advanced breast cancer will develop bone metastases for which there is no cure. Mesenchymal Stem Cells (MSCs) and their derivative osteoblasts are subpopulations of cells within the bone marrow environment, postulated as potential interacting targets for disseminating cance...

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Bibliographic Details
Published in:International journal of cancer 2009-01, Vol.124 (2), p.326-332
Main Authors: Molloy, Alan P., Martin, Fiachra T., Dwyer, Roisin M., Griffin, Tomas P., Murphy, Mary, Barry, Frank P., O'Brien, Timothy, Kerin, Michael J.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bone and Bones - metabolism
Bone and Bones - pathology
bone metastases
breast cancer
Breast Neoplasms - metabolism
Cell Culture Techniques
Cell Differentiation
Cell Line, Tumor
Cell Movement
Chemokine CCL2 - metabolism
Chemokines - metabolism
Coculture Techniques
Culture Media, Conditioned - pharmacology
differentiation
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Models, Biological
monocyte chemotactic protein‐1
Neoplasm Metastasis
Osteoblasts - metabolism
Tumors
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Summary:Over 70% of patients with advanced breast cancer will develop bone metastases for which there is no cure. Mesenchymal Stem Cells (MSCs) and their derivative osteoblasts are subpopulations of cells within the bone marrow environment, postulated as potential interacting targets for disseminating cancer cells because of their ability to secrete a range of chemokines. This study aimed to investigate chemokine secretion throughout MSC differentiation into osteoblasts and their effect on the breast cancer cells. Primary MSCs and osteoblast progenitors were cultured in appropriate conditions to induce differentiation into mature osteoblasts. Chemokines secreted throughout differentiation were detected using ChemiArray and ELISA. Migration of breast cancer cells in response to the bone‐derived cells was quantified using Transwell inserts. Breast cancer cells were cocultured with MSCs, retrieved using magnetic beads, and changes in CCL2 expression were analyzed. MSCs secreted a range of factors including IL‐6, TIMP‐1 and CCL2, the range and level of which changed throughout differentiation. CCL2 secretion by MSCs increased significantly above control cells as they differentiated into mature osteoblasts (p < 0.05). The bone‐derived cells stimulated migration of breast cancer cells, and this was inhibited (21–50%) in the presence of a CCL2 antibody. CCL2 gene expression in breast cancer cells was upregulated following direct coculture with MSCs. The varying levels of chemokines secreted throughout MSC differentiation may play an important role in supporting tumor cell homing and progression. These results further highlight the distinct effect MSCs have on breast cancer cells and their potential importance in supporting development of metastases. © 2008 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.23939