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Observation of ovarian cancer stem cell behavior and investigation of potential mechanisms of drug resistance in three-dimensional cell culture

Paper ID Volume ID Publish Year Pages File Format Full-Text
20355 43170 2014 9 PDF Available
Title
Observation of ovarian cancer stem cell behavior and investigation of potential mechanisms of drug resistance in three-dimensional cell culture
Abstract

•We demonstrate the HO8910 CD44+CD117+cells posses EOC CSC characteristics.•Using 3D culture model could accurately display EOC CSC behavior in vitro.•CD44+CD117+CSCs exhibit high chemoresistant to 5Fu, cisplatin in 3D versus 2D culture.•EOC CSC high chemoresistance are associated with high expression of ABCG2 and MMP-2.•3D model improves the efficacy of screening anticancer drugs for treatment of EOC CSCs.

Cancer cells behave differently in a three-dimensional (3D) cell culture compared with in the conventional two-dimensional (2D) one. Accumulated evidences indicate that the characteristics of cancer stem cells (CSCs) are different from common cancer cells due to their ability to produce tumors and resist chemoradiation. The objective of this work was to observe CSC behavior and investigate the potential mechanisms of CSC drug resistance in 3D versus 2D in vitro environment. We first demonstrated that the CD44+CD117+cells isolated from the human epithelial ovarian cancer HO8910 cell line have the properties of CSCs that revealed faster growth, larger tumorsphere and stronger survival potential in the hypoxic environment in 3D cell culture as well as more powerful tumorigenicity in a xenograft mice than the HO8910 cells. The CD44+CD117+CSCs also exhibited high chemoresistance to anticancer drugs when the cells were incubated with 5-fluorouracil, cisplatin and carboplatin, respectively in 3D versus 2D environment. This might be associated with the high expression of ABCG2, ABCB1 and the high expression of MMP-2 and MMP-9 in CD44+CD117+CSCs. Overall, these results suggest the advantages of using 3D culture model to accurately display CSC behavior in vitro. 3D model may improve the efficacy of screening anticancer drugs for treatment of ovarian CSCs.

Keywords
Three-dimensional culture; Epithelial ovarian cancer; Cancer stem cells; Chemoresistance; Two-dimensional culture
First Page Preview
Observation of ovarian cancer stem cell behavior and investigation of potential mechanisms of drug resistance in three-dimensional cell culture
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 118, Issue 2, August 2014, Pages 214–222
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering