Characterization and Targeting of the Aldehyde Dehydrogenase Subpopulation in Ovarian Cancer
Abstract
Despite a common outstanding response to primary therapy, most ovarian cancer patients will experience recurrence due to what is often microscopic undetectable disease. One possible cause of this is a chemoresistant population of cells with stem cell characteristics. We have examined one potential population in particular, the ALDH-positive population. We have shown that ALDH1A1-positive cells are more tumorigenic than ALDH1A1-negative cells, contribute to poor patient outcomes, and contribute to chemoresistance. Importantly, these effects can be reversed by downregulating ALDH1A1 expression with nanoparticle-delivered siRNA. Additionally, we have shown that CSCs are clinically significant, in that chemoresistant tumors have increased density of ALDH and CD133 cells. Thus they likely represent at least part of the chemoresistant population within a heterogeneous tumor. Importantly, they do not seem to explain the entire story, as there are still many CSC-negative cells present at the conclusion of treatment. Additional studies will be performed to determine which other cell types may be present in chemoresistant tumors, and which pathways or mechanisms may be mediating this resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA569964
Entities
People
- Charles N. Landen Jr.
Organizations
- University of Alabama