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Bone Microenvironment Tissue Surrogates Engineered for Reporting of Metastasized Breast Cancer Osteolytic Activity

Published online by Cambridge University Press:  22 January 2014

Jerald E. Dumas ,
Akia N. Parks  and
Manu O. Platt
Jerald E. Dumas
Affiliation:
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
Akia N. Parks
Affiliation:
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
Manu O. Platt
Affiliation:
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Dr. Suite 1308, Atlanta, GA 30332, U.S.A.
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Abstract

Breast cancer metastasis to bone continues to be a major clinical problem, and patient-to-patient variability in rates of disease progression and metastasis complicate treatment even further. This may be due to differences in the cancer cells, the osteoclasts, or the pre-metastatic niche, but all of these contribute to proteolytic remodeling necessary for osteolytic lesion establishment, primarily through secretion of cathepsin K, the most powerful human collagenase. There is debate about the relative contributions of breast cancer cells and osteoclasts and synergism between the two in altering the biochemical and biomechanical properties of the colonized bone, as these are difficult to parse with animal models. To quantify the relative contributions of breast cancer cells and osteoclasts in bone resorption, we have been developing engineered bone microenvironment tissue surrogates by adapting a poly(ester urethane) urea system embedded with microbone particles. Here, we report their use with MDA-MB-231 breast cancer cells and RAW264.7 derived osteoclasts, to provide temporal, multiscale reporters of bone resorption that can be measured non-destructively: 1) collagen degradation measured by C-terminal collagen fragment release, 2) mineral dissolution by measuring calcium released with the calcium arsenazo assay, and also show their beneficial effects in upregulating cathepsin K expression compared to tissue culture polystyrene controls. These more natural derived bone surrogates may be useful tools in mimicking bone metastatic niche and determining differences between proteolytic activity of different patients’ tumor and bone resident cells in a controlled manner.

Keywords

biomaterialbonecomposite
Type
Articles
Information
MRS Online Proceedings Library (OPL) , Volume 1625: Symposium I – Multiscale Materials in the Study and Treatment of Cancer , 2014 , mrsf13-1625-i01-04
Copyright
Copyright © Materials Research Society 2014 

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