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Microvesicle Induction of Prostate Specific Gene Expression in Normal Human Bone Marrow Cells
Michael Del Tatto, BS1, Joseph F. Renzulli, III, MD2, Gerri Dooner, BS1, Lisa Goldstein, MD2, Mark Dooner, BS1, Gerald Colvin, DO1, Devasis Chatterjee, Ph.D.1, Peter J. Quesenberry, MD1.
1Rhode Island Hospital, Providence, RI, USA, 2The Miriam Hospital, Providence, RI, USA.

Background: Transfer of genetic material from cancer cells to normal cells has been demonstrated by way of microvesicles. Cell specific phenotypes can be induced in normal cells by the transfer of material within the microvesicles leading to genetic changes. We report the identification and expression of
prostate specific genes in normal human marrow cells co-cultured with human prostate cancer cells.
Methods: Prostate tissue was harvested from 11 patients with prostate cancer. In 4 cases, prostate tissue was co cultured across from human marrow for 2 or 7 days, but separated from it by a 0.4μM polystyrene membrane. Alternatively, in 5 cases, conditioned media from the patients cancer tissue was collected, ultracentrifuged, and microvesicles collected for co cultures (3 cases), or vesicle
characterization (3 cases). Explanted, human marrow was harvested from cultures, RNA extracted, and real time RT-PCR performed for select prostate specific genes.
Results: Marrow exposed to human prostate tumor (4 cases) or isolated microvesicles (3 cases) in culture showed at least a 2 fold or greater expression of prostate genes as compared to control marrow.In one case in which normal prostate was co cultured, there were no prostate gene elevations in
normal marrow.
Conclusions: Prostate cancer tumor cells co-cultured with human bone marrow cells induce expression of prostate specific genes. The proposed mechanism of transfer of the genetic material is via microvesicles. This mechanism presents an opportunity for novel therapeutic agents such as antibodies to block microvesicle release from cancer cells or agents which may block cells from accepting microvesicles.


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