An in vitro model of prostate cancer bone metastasis for highly metastatic and non-metastatic prostate cancer using nano
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MRS Advances © 2019 Materials Research Society DOI: 10.1557/adv.2018.682
An in vitro model of prostate cancer bone metastasis for highly metastatic and non-metastatic prostate cancer using nanoclay bone-mimetic scaffolds MD Shahjahan Molla1, Dinesh R. Katti1, and Kalpana S. Katti1 1
Civil and Environmental Engineering, North Dakota State University, Fargo, ND 58108, USA
ABSTRACT
Prostate cancer has a strong preference for metastasizing to bone which is the primary cause of prostate cancer-related morbidity and mortality. The complex nature of cancer metastasis requires the development of translational models that recapitulate a specific metastatic stage. Herein, we report the mimicking of mesenchymal to epithelial transition (MET) of prostate cancer cells using highly metastatic and a non-metastatic prostate cancer cell lines. A unique cell culture technique that we termed as ‘sequential culture’ was used to create a biomimetic bone microenvironment for metastasized prostate cancer cells by introducing bioactive factors from osteogenic induction of human mesenchymal stem cells (MSCs) within the porous 3D scaffolds. The in vitro 3D tumor model can be used as a testbed to study the interaction between prostate cancer and bone microenvironment and for the design of novel therapeutic studies.
INTRODUCTION Cancer-associated deaths are mostly attributed to metastasis, a process in which cancer spreads from its place of origin to other parts of the body, yet the mechanism of cancer metastasis remains ill understood. A complex metastatic cascade is involved in the dissemination of cancer cells to the distant organ. It includes the sequence of phases: local invasion, intravasation, circulation, arrest and extravasation, proliferation and angiogenesis. Two very significant events take place during this complex cascade that are epithelial to mesenchymal transition (EMT), and mesenchymal to epithelial transition (MET) where cell phenotype changes between epithelial to mesenchymal state and viceversa. Mesenchymal cells undergo a series of events during MET, including gaining of apical-basal polarity, an aggregation of previously disbanded mesenchymal cells, and reorganization of cytoskeletal features. Considering the critical role that MET plays in
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metastasis, understanding the molecular mechanisms of MET offers new hope for inhibiting tumor formation and developing anti-cancer therapeutics. In the event of localized and regional prostate cancer the 5-year survival is 100%, but for the distant organ, it is only 30%[1]. The strong preference of prostate cancer for metastasizing to bone is the principal cause of prostate cancer-related morbidity and mortality. Currently, there is no cure for bone metastasized prostate cancer due to lack of understanding of the mechanism that underl
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