Abstract 5399: Mechanism of efficient eradication of castration-resistant human prostate cancer cells by inactivated Sendai virus particle
Authors: Hatano Koji , Nakai Yasutomo , Miyamoto Yasuhide , Kaneda Yasufumi , Nonomura Norio 
Published: June 2012

Abstract
Castration-resistant prostate cancer is one of the intractable human cancers in the world. Here, we examined the mechanism of direct tumor killing activity of inactivated Sendai virus particle [hemagglutinating virus of Japan envelope (HVJ-E)] in castration-resistant human prostate cancer cells. HVJ-E can induce apoptosis in castration-resistant human prostate cancer cells, PC3 and DU145, but not in hormone-sensitive human prostate cancer cells, LNCap or normal prostate epithelium PNT2. Preferential binding of HVJ-E to PC3 and DU145 over LNCap and PNT2 was observed, because PC3 and DU145 produced high amount of viral receptor gangliosides such as GD1a and sialyl paragloboside (SPG) compared with LNCap and PNT2. After HVJ-E treatment, retinoic acid-inducible gene-I (RIG-I) helicase which activates Type I IFN expression was up-regulated in PC3 cells. Produced type I IFN enhanced caspase 8 expression via Janus kinases/Signal Transducers and Activators of Transcription pathway, activated caspase 3 and induced apoptosis in cancer cells. Transfection of Poly:IC (polyinosinic:polycytidylic acid) induced apoptosis in LNCap cells as well as PC3 cells. Thus, the preferential binding of HVJ-E to cancer cells using viral receptor gangliosides and the production of type I IFN after activation of RIG-I induced by fragmented RNA of HVJ-E are thought to be the pivotal mechanisms of direct tumor killing activity of HVJ-E in castration-resistant prostate cancer cells. When HVJ-E was directly injected into a mass of PC3 tumor cells in SCID (severe combined immunodeficiency) mice, a marked reduction in the bulk of each tumor mass was observed. Although co-injection of an anti-asialo GM1 antibody with HVJ-E into each tumor mass slightly attenuated the tumor suppressive activity of HVJ-E, significant suppression of tumor growth by HVJ-E was observed even in the presence of anti-asialo GM1 antibody. This suggests that the regression of castration-resistant prostate cancers in mice was partially due to the activation of natural killer cells and mainly caused by direct tumor killing activity of HVJ-E. HVJ-E can infect cancer cells using viral receptor gangliosides. Castration-resistant prostate cancer cells, PC3 and DU145, produced high amount of GD1a and SPG, the receptor of HVJ-E, compared with LNCap and PNT2. We hypothesized that sialyltransferases which produce GD1a and SPG are up-regulated in castration-resistant prostate cancer cells. Transcriptional factors such as AP-1 or NF-κB are up-regulated in castration-resistant prostate cancers. We also examined transcriptional regulation of sialyltransferases which are involved in production of GD1a and SPG.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5399. doi:10.1158/1538-7445.AM2011-5399