Tissue ‐engineered nanoclay based 3D in vitro breast cancer model for studying breast cancer metastasis to bone

AbstractBreast cancer (BrCa) preferentially spreads to bone and colonizes within the bone marrow to cause bone metastases. To improve the outcome of patients with breast cancer bone metastasis, we need to understand better the mechanisms underlying bone metastasis. Researchers have relied heavily uponin vivo xenografts due to limited availibility of human bone metastasis samples. A significant limitation of these is that they do not have a human bone microenvironment. To address this issue, we have developed a nanoclay based 3Din vitro model of breast cancer bone metastasis using human breast cancer cells mimicking late stage of breast cancer pathogenesis at the metastatic site. This 3D model can provide a microenvironment suitable for cell ‐cell, and cell‐matrix interactions while retaining the behavior of BrCa cells with different metastasis potential (i.e., highly metastatic MDA‐MB‐231, and low metastatic MCF‐7) as shown by the production of alkaline phosphatase (ALP) and matrix metalloproteinase‐9 (MMP‐9). The sequent ial culture of mesenchymal stem cells (MSCs) with MCF‐7 exhibited 3D tumoroids formation and also occurrence of mesenchymal to epithelial transition of cancer metastasis as evidenced by gene expression and immunocytochemistry. The unique and distinct behavior of highly metastatic MDA‐MB‐231 an d the low metastatic MCF‐7 was observed at the bone metastasis site. The changes to migratory capabilities and invasiveness in MDA‐MB‐231 in ...
Source: Journal of Tissue Engineering and Regenerative Medicine - Category: Biotechnology Authors: Tags: RESEARCH ARTICLE Source Type: research