Objectives While most women with ovarian cancer will achieve complete remission after treatment, the majority will relapse within two years, highlighting the need for novel therapies. Cancer stem cells (CSC) have been identified in ovarian cancer and most other carcinomas as a small population of cells that can self-renew. CSC are more chemoresistant and radio-resistant than the bulk tumor cells; it is likely that CSC are responsible for relapse, the major problem in cancer treatment. CD133 has emerged as one of the most promising markers for CSC in ovarian cancer. The hypothesis driving this study is that despite their low numbers in ovarian cancer tumors, CSC can be eradicated using CD133 targeted therapy and tumor growth can be inhibited. Methods Ovarian cancer cell lines were evaluated using flow cytometry for expression of CD133. In vitro viability studies with an anti-CD133 targeted toxin were performed on one of the cell lines, NIH:OVCAR5. The drug was tested in vivo using a stably transfected luciferase-expressing NIH:OVCAR5 subline in nude mice, so that tumor growth could be monitored by digital imaging in real time. Results Ovarian cancer cell lines showed 5.6% to 16.0% CD133 expression. dCD133KDEL inhibited the in vitro growth of NIH:OVCAR5 cells. Despite low numbers of CD133-expressing cells in the tumor population, intraperitoneal drug therapy caused a selective decrease in tumor progression in intraperitoneal NIH:OVCAR5-luc tumors. Conclusions Directly targeting CSC that are a major cause of drug resistant tumor relapse with an anti-CD133 targeted toxin shows promise for ovarian cancer therapy.
Bibliographical noteFunding Information:
This work was supported in part by the Minnesota Ovarian Cancer Alliance , US Public Health Service Grant R01-CA36725 awarded by the NCI and the NIAID, DHHS, and the Randy Shaver Foundation. This work was also supported in part by NIH P30 CA77598 utilizing the following Masonic Cancer Center, University of Minnesota shared resources: the Flow Cytometry Core Facility and the Comparative Pathology Core Facility. We thank Drs. Vanderhyden and Ramakrishnan for the cell lines.
- Cancer stem cells
- Ovarian cancer
- Targeted toxin
- Xenograft model