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Breast Cancer Res Treat (2011) 126:7383 DOI 10.1007/s10549-010-0889-9
PRECLINICAL STUDY
Interactions between breast cancer cells and bone marrow derived cells in vitro dene a role for osteopontin in affecting breast cancer cell migration
Konstantin Koro Stephen Parkin Brant Pohorelic
An-Dao Yang Aru Narendran Cay Egan
Anthony Magliocco
Received: 11 January 2010 / Accepted: 3 April 2010 / Published online: 17 April 2010 Springer Science+Business Media, LLC. 2010
Abstract The preferential metastasis of breast cancer cells to bone is a complex set of events including homing and preferential growth which may include unique factors produced by bone cells in the immediate microenvironment. In this study, we evaluated the suitability of bone cells derived from orthoplastic surgeries for use in an in vitro co-culture system representing a model of the bone microenvironment. Using a limiting dilution assay we determined the relative survival and proliferation potentials of breast cancer cell lines co-cultured on bone-derived cells or on Hs68 broblasts. The comparison of bone and skin broblastic substrata indicates that MCF-7 cells preferentially survive and grow in a bone microenvironment (P \ 0.001). Overall, we show that bone-derived cells enhance survival, proliferation, and migration of breast cancer cells, where migration is in part mediated by bone cell-produced osteopontin. Our in vitro co-culture model system provides a robust cost-effective method to study the various factors that mediate cancer/bone-derived cell interactions.
Keywords Breast cancer Bone metastasis
In vitro co-culture system Tumour microenvironment
Osteopontin
Introduction
Breast cancer is a common malignancy in women and can have devastating effects on patients and their families. About 70% of patients with advanced breast cancer develop skeletal metastases, resulting in low quality of life due to severe pain, hypercalcemia, pathological bone fractures and spinal cord compression [13]. Bone metastases are rarely a direct cause of cancer mortality and a patient may survive for years with skeletal disease [3]. The economic impact of the increased costs of treatment of patients with distant breast cancer metastasis is also substantial [4].
As early as 1889, Stephen Paget observed that some cancers metastasized preferentially to specic organs, and developed his theory of seed and soil [5]. The essential tenet of this theory was that cancer cells (seeds) disseminate throughout the body from their point of origin but can only set...