Naslov
Transformed Rat Prostate Cell-Derived Microvesicles Support Immune Evasion

Autori
Mills, David R. ; Yang, DongQin ; Callanan, Helen M. ; Brilliant, Kate E. ; Wan, Yinsheng ; Srajer Gajdosik, Martina ; Josić, Djuro ; Hixson, Douglas C.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book of International Symposium of Cellular Vesicles: Determination of Cell Fate / - , 2011

Skup
International Symposium of Cellular Vesicles: Determination of Cell Fate

Mjesto i datum
Providence (RI), Sjedinjene Američke Države, 21.04.2011. - 22.04.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
prostate cancer; immune invasion; spontaneous transformation; natural killer cells

Sažetak
Prostate cancer is the most common cancer among males excluding skin cancers. In the United States alone, in 2010 approximately 217, 730 men will be diagnosed with new cases of prostate cancer and 32, 050 men will die of this cancer. To date, the critical molecular and cellular mechanisms involved in the development and progression of prostate cancer remain elusive. We have developed an in vitro model of spontaneous transformation using rat prostate epithelial cells (PEC) that culminates at high passage (p>85) in anchorage independent growth when plated on soft agar, a well-described hallmark of cellular transformation. High passage anchorage independent PEC formed large tumors when injected into immunodeficient mice. In contrast, low passage PEC did not. Of particular interest, we have identified a small subpopulation of cells derived from the high passage anchorage independent cells that migrate through the soft agar and expand on the underlying plastic substratum. Preliminary data suggest that the high passage and soft agar invasive (SAI) cells have increased motility and chemoresistance to paclitaxel as compared to low passage anchorage dependent PEC. Using indirect immunofluorescence, we identified a marker, OC.2 that was expressed by a low percentage of low and high passage PEC but was expressed by 100% of freshly isolated SAI cells. Conversely, two additional markers, OC.4 and OC.5, were expressed by a high percentage of low and high passage PEC but were absent in SAI cells. We have also shown that low, high and SAI PEC shed high levels of Necl-5 positive microvesicles. Necl-5, a cell surface adhesion molecule often overexpressed in many epithelial carcinomas, is also a known ligand for CD226, a potent inducer of cytotoxic activity expressed by natural killer (NK) cells. Preliminary data has demonstrated that pre- incubation of NK cells with Necl-5 positive microvesicles isolated from SAI-derived PEC significantly suppressed NK cytotoxicity. In contrast, microvesicles purified from low passage PEC had no affect on NK cytotoxicity.

Izvorni jezik
Engleski

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