Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden

Abubaker, K., Latifi, A., Luwor, R., Nazaretian, S., Zhu, H., Quinn, M.A., Thompson, E.W., Findlay, J.K., & Ahmed, N. (2013) Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden. Molecular Cancer, 12(24).

View at publisher (open access)


Over 80% of women diagnosed with advanced-stage ovarian cancer die as a result of disease recurrence due to failure of chemotherapy treatment. In this study, using two distinct ovarian cancer cell lines (epithelial OVCA 433 and mesenchymal HEY) we demonstrate enrichment in a population of cells with high expression of CSC markers at the protein and mRNA levels in response to cisplatin, paclitaxel and the combination of both. We also demonstrate a significant enhancement in the sphere forming abilities of ovarian cancer cells in response to chemotherapy drugs. The results of these in vitro findings are supported by in vivo mouse xenograft models in which intraperitoneal transplantation of cisplatin or paclitaxel-treated residual HEY cells generated significantly higher tumor burden compared to control untreated cells. Both the treated and untreated cells infiltrated the organs of the abdominal cavity. In addition, immunohistochemical studies on mouse tumors injected with cisplatin or paclitaxel treated residual cells displayed higher staining for the proliferative antigen Ki67, oncogeneic CA125, epithelial E-cadherin as well as cancer stem cell markers such as Oct4 and CD117, compared to mice injected with control untreated cells. These results suggest that a short-term single treatment of chemotherapy leaves residual cells that are enriched in CSC-like traits, resulting in an increased metastatic potential. The novel findings in this study are important in understanding the early molecular mechanisms by which chemoresistance and subsequent relapse may be triggered after the first line of chemotherapy treatment.

Impact and interest:

56 citations in Scopus
Search Google Scholar™
46 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

Full-text downloads:

122 since deposited on 07 May 2014
65 in the past twelve months

Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.

ID Code: 71138
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):6 Export Date: 6 May 2014 Source: Scopus Art. No.: 24 PubMed ID: 23537295
Keywords: Ascites, Cancer stem cell, Chemoresistance, Metastasis, Ovarian carcinoma, Recurrence
DOI: 10.1186/1476-4598-12-24
ISSN: 1476-4598
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2013 Abubaker et al.; licensee BioMed Central Ltd.
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 07 May 2014 02:02
Last Modified: 08 May 2014 02:38

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page