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01-10-2008 | Research Paper

Epithelial to mesenchymal transition (EMT) in human prostate cancer: lessons learned from ARCaP model

Authors: Haiyen E. Zhau, Valerie Odero-Marah, Hui-Wen Lue, Takeo Nomura, Ruoxiang Wang, Gina Chu, Zhi-Ren Liu, Binhua P. Zhou, Wen-Chin Huang, Leland W. K. Chung

Published in: Clinical & Experimental Metastasis | Issue 6/2008

Abstract

Androgen refractory cancer of the prostate (ARCaP) cells contain androgen receptor (AR) and synthesize and secrete prostate specific antigen (PSA). We isolated epithelia-like ARCaP_E from parental ARCaP cells and induced them to undergo epithelial–mesenchymal transition (EMT) by exposing these cells to soluble factors including TGFβ1 plus EGF, IGF-1, β2-microglobulin (β2-m), or a bone microenvironment. The molecular and behavioral characteristics of the resultant ARCaP_M were characterized extensively in comparison to the parental ARCaP_E cells. In addition to expressing mesenchymal biomarkers, ARCaP_M gained 100% incidence of bone metastasis. ARCaP_M cells express receptor activator of NF-κB ligand (RANKL), which was shown to increase tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in culture, and when metastatic to bone in vivo. We provide evidence that RANKL expression was promoted by increased cell signaling mediated by the activation of Stat3-Snail-LIV-1. RANKL expressed by ARCaP_M cells is functional both in vitro and in vivo. The lesson we learned from the ARCaP model of EMT is that activation of a specific cell signaling pathway by soluble factors can lead to increased bone turnover, mediated by enhanced RANKL expression by tumor cells, which is implicated in the high incidence of prostate cancer bone colonization. The ARCaP EMT model is highly attractive for developing new therapeutic agents to treat prostate cancer bone metastasis.

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Title: Epithelial to mesenchymal transition (EMT) in human prostate cancer: lessons learned from ARCaP model
Authors: Haiyen E. Zhau
Valerie Odero-Marah
Hui-Wen Lue
Takeo Nomura
Ruoxiang Wang
Gina Chu
Zhi-Ren Liu
Binhua P. Zhou
Wen-Chin Huang
Leland W. K. Chung
Publication date: 01-10-2008
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 6/2008
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-008-9183-1

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