AIMS: To examine the presence of satellite cells in human urethral rhabdosphincter (RS) and to clarify the growth mechanism of these cells. METHODS: Human RS was obtained from patients undergoing radical prostatectomy for prostate cancer. Primary cells were selectively cultured by magnetic affinity cell sorting (MACS) using an anti-neural cell adhesion molecule (NCAM) antibody. Selectively cultured cells, transfected with simian virus-40 T antigen to extend their lifespan, were used for the following experiments: (1) determination of the effects of hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (b-FGF); (2) clarification of the signal transduction pathways used by these growth factors; and (3) examination of the autocrine actions in these cells. RESULTS: Selectively cultured cells expressed striated muscle markers and could differentiate into myotubes. HGF and IGF-1 stimulated the growth of these cells in a dose-dependent fashion. Regarding signal transduction, HGF phosphorylated ERK1/2 for 120 min while only transiently modifying Akt. In contrast, IGF-1 phosphorylated Akt but not ERK1/2. Furthermore, these cells produced transcripts and proteins for both HGF and IGF-1, and anti-HGF and anti-IGF-1 antibodies suppressed cell proliferation. CONCLUSIONS: Satellite cells are present in human RS. The proliferation of these cells is primarily enhanced through both the endogenous and exogenous actions of HGF and IGF-I via ERK1/2 and Akt. These findings may be useful in the development of a novel technique for the regeneration of human RS to treat urinary incontinence. Copyright (c) 2007 Wiley-Liss, Inc.
AIMS: To examine the presence of satellite cells in humanurethral rhabdosphincter (RS) and to clarify the growth mechanism of these cells. METHODS:Human RS was obtained from patients undergoing radical prostatectomy for prostate cancer. Primary cells were selectively cultured by magnetic affinity cell sorting (MACS) using an anti-neural cell adhesion molecule (NCAM) antibody. Selectively cultured cells, transfected with simian virus-40 T antigen to extend their lifespan, were used for the following experiments: (1) determination of the effects of hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (b-FGF); (2) clarification of the signal transduction pathways used by these growth factors; and (3) examination of the autocrine actions in these cells. RESULTS: Selectively cultured cells expressed striated muscle markers and could differentiate into myotubes. HGF and IGF-1 stimulated the growth of these cells in a dose-dependent fashion. Regarding signal transduction, HGF phosphorylated ERK1/2 for 120 min while only transiently modifying Akt. In contrast, IGF-1 phosphorylated Akt but not ERK1/2. Furthermore, these cells produced transcripts and proteins for both HGF and IGF-1, and anti-HGF and anti-IGF-1 antibodies suppressed cell proliferation. CONCLUSIONS: Satellite cells are present in human RS. The proliferation of these cells is primarily enhanced through both the endogenous and exogenous actions of HGF and IGF-I via ERK1/2 and Akt. These findings may be useful in the development of a novel technique for the regeneration of human RS to treat urinary incontinence. Copyright (c) 2007 Wiley-Liss, Inc.
Authors: Brian P Rubin; Koichi Nishijo; Hung-I Harry Chen; Xiaolan Yi; David P Schuetze; Ranadip Pal; Suresh I Prajapati; Jinu Abraham; Benjamin R Arenkiel; Qing-Rong Chen; Sean Davis; Amanda T McCleish; Mario R Capecchi; Joel E Michalek; Lee Ann Zarzabal; Javed Khan; Zhongxin Yu; David M Parham; Frederic G Barr; Paul S Meltzer; Yidong Chen; Charles Keller Journal: Cancer Cell Date: 2011-02-15 Impact factor: 31.743