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Delineating breast cancer cell interactions with engineered bone microenvironments
Author(s) -
Taubenberger Anna V,
Quent Verena M,
Thibaudeau Laure,
Clements Judith A,
Hutmacher Dietmar W
Publication year - 2013
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.1875
Subject(s) - osteopontin , extracellular matrix , integrin , cell culture , microbiology and biotechnology , cell , extracellular , cancer cell , bone metastasis , cancer research , chemistry , secretion , bone cell , type i collagen , biology , cell migration , bone disease , metastasis , cancer , immunology , endocrinology , biochemistry , osteoporosis , genetics
The mechanisms leading to colonization of metastatic breast cancer cells (BCa) in the skeleton are still not fully understood. Here, we demonstrate that mineralized extracellular matrices secreted by primary human osteoblasts (hOBM) modulate cellular processes associated with BCa colonization of bone. A panel of four BCa cell lines of different bone‐metastatic potential (T47D, SUM1315, MDA‐MB‐231, and the bone‐seeking subline MDA‐MB‐231BO) was cultured on hOBM. After 3 days, the metastatic BCa cells had undergone morphological changes on hOBM and were aligned along the hOBM's collagen type I fibrils that were decorated with bone‐specific proteins. In contrast, nonmetastatic BCa cells showed a random orientation on hOBM. Atomic force microscopy‐based single‐cell force spectroscopy revealed that the metastatic cell lines adhered more strongly to hOBM compared with nonmetastatic cells. Function‐blocking experiments indicated that β 1 ‐integrins mediated cell adhesion to hOBM. In addition, metastatic BCa cells migrated directionally and invaded hOBM, which was accompanied by enhanced MMP‐2 and ‐9 secretion. Furthermore, we observed gene expression changes associated with osteomimickry in BCa cultured on hOBM. As such, osteopontin mRNA levels were significantly increased in SUM1315 and MDA‐MB‐231BO cells in a β 1 ‐integrin–dependent manner after growing for 3 days on hOBM compared with tissue culture plastic. In conclusion, our results show that extracellular matrices derived from human osteoblasts represent a powerful experimental platform to dissect mechanisms underlying critical steps in the development of bone metastases.