In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 3204-3204
Abstract:
Cellular dormancy refers to a state of quiescence during metastatic progression, in which disseminated tumor cells enter cell cycle arrest. Such dormant cells are thought to influence cancer drug sensitivity, and strategies have hence emerged to target dormant cells for novel therapeutic approaches. Mechanisms of cellular dormancy remain poorly understood, with current evidence suggesting a major role of the metastatic microenvironment in deciding cell fate. Research in this area, however, is hampered by the lack of appropriate experimental models of cancer cell dormancy. Here, we described the use of tissue engineering methods to generate an in vitro model of bone-metastatic disease. Briefly, human fetal mesenchymal stem cell (hfMSC) and human umbilical vein endothelial cell (HUVEC) were co-cultured to respectively represent the osteo-progenitor and vascular compartments, and subsequently induced to form a vascularized bone marrow model. Metastatic prostate cancer PC3 cells were then added to simulate metastatic dissemination and the co-culture was maintained for 28 days. Reporter genes were employed to facilitate live-monitoring of HUVEC and PC3 cells in the co-culture. Using this system, we observed single cell dormancy, particularly when osteogenic induction was performed. Additionally, PC3 cells were observed to exert osteo-modulatory effects on the engineered bone microenvironment. Immunostaining for cellular markers indicated low expression of proliferation marker Ki-67 and various mesenchymal markers, indicating absence of Epithelial-Mesenchymal Transition (EMT). Dormancy was functionally assessed by retrieving the PC3 cells and subsequently replating under normal culture conditions to rescue cellular proliferation. Finally, drug sensitivity assays demonstrated reduced susceptibility of dormant cells to conventional chemotherapeutic drugs. This in vitro model of prostate cancer cell dormancy in the engineered bone marrow may thus be useful for furthering our understanding of cellular dormancy, and may further provide a useful tool for drug testing. Citation Format: Yanwan Liao, Jun Jie Aaron Tan, Sahaana Tamilselvan, Jerry Chan, Ruowen Ge, Lui Shiong Lee, Mark Chong. Tissue engineered models of metastatic bone disease for the study of prostate cancer cell dormancy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3204. doi:10.1158/1538-7445.AM2015-3204
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-3204
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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