In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 19_Supplement ( 2013-10-01), p. C53-C53
Abstract:
Jagged1, a NOTCH ligand, has been shown to correlate with poor prognosis and metastasis of prostate cancer (CaP). CaP is a leading cause of cancer death among men worldwide. There is currently no effective therapeutic strategy for patients with castration-resistant prostate cancer (CRPC) which is defined as continued growth of CaP despite the suppression of male hormones. We previously reported that recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus causes cell apoptosis of PC-3, a CRPC, via integrin β1 in vitro. Herein, we demonstrate that rVP1 inhibited cell migration/invasion at a non-toxic concentration and reduced the expression level of Jagged1 and phosphorylation of Akt (Ser 473) and IKKα/β (Ser 176/180) of PC-3 cells in vitro. This inhibition was abolished by integrin β1 blocking antibody, knockdown of integrin β1, or a constitutively active Akt. Furthermore, intravenous administration of rVP1 induced tumor apoptosis, suppressed tumor Jagged1 expression level, reduced primary-tumor spread to lymph nodes and bone, and prolonged the survival time of tumor-bearing mice in an orthotopic PC-3 xenograft model. Recombinant VP1 retarded tumor expansion within the bone and tumor-induced osteolysis in an experimental model of bone metastasis made by injecting PC-3 cells carrying the luciferase gene into mouse left ventricle. Finally, in vivo vascular permeability analyses showed that rVP1 specifically targeted tumor cells by penetrating leaky tumor vasculature. Recombinant VP1 may thus suppress Jagged1 expression of CaP cells by inhibiting the integrin β1/Akt/NF-κB signaling pathway to attenuate expansion of bone metastases and tumor-induced osteolysis in CRPC. Citation Format: Jui-Ling Wang, Shao-Wen Hung, Chi-Ming Liang, Pei-Wen Hsiao, Shu-Mei Liang. rVP1 inhibits prostate cancer metastasis via suppression of Jagged1. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C53.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.FBCR13-C53
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
Bookmarklink