Evaluating the Potential of Adipose Tissue-Derived MSCs as Anticancer Gene Delivery Vehicles to Bone-Metastasized Prostate Cancer
Annual rept. 1 Apr 2009-31 Mar 2010
TULANE UNIV NEW ORLEANS LA
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The purpose of this project is to demonstrate that adipose tissue derived MSCs AT-MSCs have tumor-homing potential and can be used to deliver anti-cancer genes to bone metastasized prostate cancer PCa cells. The ease of isolation, culturing and genetic transduction of ATMSCs make them attractive candidates for gene-therapy approaches against cancers. The purpose of our proposed studies is to enrich for those AT-MSCs which have better tumor-homing potential and demonstrate that these enriched AT-MSCs carrying a suicide gene HSV-TK will localize to PCa tumor foci within the bone and chemosensitize the cancer cells to ganciclovir GCV. We have obtained several stocks of primary AT-MSCs and characterized them for their mesenchymal stem cell lineage. We have succeeded in stably transducing them with a fluorescent reporter GFP. In trans-well in vitro studies, we have isolated cells with enhanced tumor-homing potential and have been able to increase their invasion and migration towards tumor-derived factors. We have enriched these subpopulations and have initiated their GFP transduction. By gene-array analysis, we have identified several surface markers that may enable the invasive phenotype in AT-MSCs. These markers would enable us to enrich for ATMSCs as gene delivery vehicles and our approach using HSV-TKGCV would facilitate the development of an optimal anti-cancer strategy to eliminate the bone PCa foci in a tumorxenograft model in vivo.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research