Evaluating the Potential of Adipose Tissue-Derived MSCs as Anticancer Gene Delivery Vehicles to Bone-Metastasized Prostate Cancers
Abstract
Adipose tissue derived MSCs (AT-MSCs) have tumor-homing potential and can be used as anti-cancer gene delivery vehicles to prostate cancer (PCa). Our investigations have elucidated the role of factors released by both tumor cells and tumor-associated stromal cells, in increasing tran-endothelial migration (TEM) and tumor-site specific homing of AT-MSCs. We have identified several cell-surface markers that enable this phenotype of AT-MSCs, and have demonstrated a crucial role of the SDF-1/CXCR4 axis. We have also shown that tumor-derived factors increase differentiation of AT-MSCs and rapidly augment several lineage restricted transcription factor, e.g. PPAR-gamma2 and RUNX2. Our goal is to demonstrate that AT-MSCs can deliver an inducible suicide gene (HSV-TK) to tumor foci which will locally increase ganciclovir (GCV) induced killing of the PCa cells. We have used enriched AT-MSCs stably/transiently expressing the CXCR4 and/or HSV-Tk genes, and have shown their in vitro ability to induce a "bystander" killing effect in cocultured PCa cells. We have documented the tumor-homing ability of these AT-MSCs in tumor-xenografts in nude mice. We are in the process of investigating their enhanced tumor-homing property and their anti-tumor efficacy in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2011
- Accession Number
- ADA547610
Entities
People
- Debasis Mondal
Organizations
- Tulane University of Louisiana