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

Research

Simon Nazaretian¹  Hongjian Zhu²  Rod Luwor²  Erik W Thompson³  Michael A Quinn⁴  Jock K Findlay⁵  Ardian Latifi⁶  Khalid Abubaker⁶  Nuzhat Ahmed⁷ 

[1] Department of Anatomical Pathology, Royal Women’s Hospital, 3052, Victoria, Australia;Department of Surgery, University of Melbourne, Royal Melbourne Hospital, 3052, Victoria, Australia;Department of Surgery, University of Melbourne, St Vincent Hospital, Victoria, Australia;St Vincent’s Institute, 3065, Victoria, Australia;Women’s Cancer Research Centre, Royal Women’s Hospital, 3052, Victoria, Australia;Department of Obstetrics and Gynaecology, University of Melbourne, 3052, Victoria, Australia;Women’s Cancer Research Centre, Royal Women’s Hospital, 3052, Victoria, Australia;Department of Obstetrics and Gynaecology, University of Melbourne, 3052, Victoria, Australia;Prince Henry’s Institute of Medical Research, 3168, Victoria, Australia;Women’s Cancer Research Centre, Royal Women’s Hospital, 3052, Victoria, Australia;Department of Surgery, University of Melbourne, St Vincent Hospital, Victoria, Australia;Women’s Cancer Research Centre, Royal Women’s Hospital, 3052, Victoria, Australia;Department of Surgery, University of Melbourne, St Vincent Hospital, Victoria, Australia;Department of Obstetrics and Gynaecology, University of Melbourne, 3052, Victoria, Australia;Prince Henry’s Institute of Medical Research, 3168, Victoria, Australia;

关键词: Ovarian carcinoma;    Cancer stem cell;    Metastasis;    Ascites;    Chemoresistance;    Recurrence;   

DOI  :  10.1186/1476-4598-12-24

 received in 2012-12-06, accepted in 2013-03-19,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Abubaker et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.