Abstract 3843: Design of a novel three-dimensional biomimetic nano bone model for breast cancer bone metastasis and therapeutics discovery.

Abstract

Abstract Breast cancer is the leading cause of cancer-related death in American women, accounting for more than 200,000 new cases and 40,000 deaths annually. Most breast cancer patients will eventually develop complications due to bone metastasis. However, the mechanisms by which breast cancer metastasizes to bone are not well investigated. Traditional tumor metastasis models contain many inherent limitations. Therefore, the objective of this research is to design an innovative biomimetic 3D tissue engineered in vitro bone model via hydroxyapatites (HA), human bone marrow mesenchymal stem cell (hMSC) and natural chitosan hydrogel for breast cancer metastasis study and therapeutics discovery. 3D porous HA-chitosan scaffolds with different crystalline, size and concentration of HA (specifically, 10% and 20% nanocrystalline HA, microcrystalline HA and amorphous HA) were fabricated via a lyophilization procedure. Metastasis breast cancer cells MDA-MB-231 were seeded on all scaffolds and cultured for 4h, 1, 3 and 5 days. The cell adhesion and proliferation results showed that concentration, size and crystallinity of HA have a significant impact on metastasis breast cancer cell behavior. 10% nanocrystalline HA can significantly enhance breast cancer cell attachment when compared to all of other HA. Considering natural bone also consisting of nanocrystalline HA, 10% synthesized nanocrystalline HA in porous chitosan scaffold can create a more biomimetic bone environment for breast cancer bone metastasis study. Furthermore, our bone model was further modified by inducing hMSC osteogenic differentiation in the scaffold resulting in deposition of bioactive protein and calcium by MSC. SEM images of the MSC modified scaffolds revealed that protein and calcium were deposited on both its surface and inner architecture. Two different metastatic breast cancer cells with different metastasis potential (less metastatic MCF-7 and highly metastatic MDA-MB-231) were evaluated in this modified bone model in vitro. The results showed that MDA-MB-231 expanded faster than MCF-7 in the scaffold after 24h culture. Confocal microscopy was used to verify two cells metastasis ability and showed that MDA-MB-231 could migrate deeper in this modified bone model compared to MCF-7. Our results revealed that this model can well reflect the two different metastasis behaviors, making this biomimetic 3D tissue engineered nano bone model promising for future breast cancer cell metastasis study and therapeutics discovery. Citation Format: Mian Wang, Sidney W. Fu, Lijie Zhang. Design of a novel three-dimensional biomimetic nano bone model for breast cancer bone metastasis and therapeutics discovery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3843. doi:10.1158/1538-7445.AM2013-3843