Accession Number : ADA527884


Title :   Evaluating the Potential of Adipose Tissue-Derived MSCs as Anticancer Gene Delivery Vehicles to Bone-Metastasized Prostate Cancer


Descriptive Note : Annual rept. 1 Apr 2009-31 Mar 2010


Corporate Author : TULANE UNIV NEW ORLEANS LA


Personal Author(s) : Mondal, Debasis


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a527884.pdf


Report Date : Apr 2010


Pagination or Media Count : 16


Abstract : 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-TK/GCV would facilitate the development of an optimal anti-cancer strategy to eliminate the bone PCa foci in a tumorxenograft model in vivo.


Descriptors :   *GENES , *ANTIGENS , *ADIPOSE TISSUE , *BONES , *PROSTATE CANCER , METASTASIS , GENETICS , IN VIVO ANALYSIS , TRANSDUCERS


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE