title: Prostate cancer stem-like cells/cancer-initiating cells have an autocrine system of hepatocyte growth factor.
abstract: Prostate cancer cells include a small population of cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) that have roles in initiation and progression of the cancer. Recently, we isolated prostate CSCs/CICs as aldehyde dehydrogenase 1-highh (ALDH1(high) ) cells using the ALDEFLUOR assay; however, the molecular mechanisms of prostate CSCs/CICs are still elusive. Prostate CSCs/CICs were isolated as ALDH1(high) cells using the ALDEFLUOR assay, and the gene expression profiles were analyzed using a cDNA microarray and RT-PCR. We found that prostate CSCs/CICs expressed higher levels of growth factors including hepatocyte growth factor (HGF). Hepatocyte growth factor protein expression was confirmed by enzyme linked immunosorbent assay and Western blotting. On the other hand, c-MET HGF receptor was expressed in both CSCs/CICs and non-CSCs/CICs at similar levels. Hepatocyte growth factor and the supernatant of myofibloblasts derived from the prostate augmented prostasphere formation in vitro, and prostasphere formation was inhibited by an anti-HGF antibody. Furthermore, c-MET gene knockdown by siRNA inhibited the prostasphere-forming ability in vitro and tumor-initiating ability in vivo. Taken together, the results indicate that HGF secreted by prostate CSCs/CICs and prostate myofibroblasts has a role in the maintenance of prostate CSCs/CICs in an autocrine and paracrine fashion.
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Sachiyo
authors: S
authors: Nishida
authors: Yoshihiko
authors: Y
authors: Hirohashi
authors: Toshihiko
authors: T
authors: Torigoe
authors: Ryuta
authors: R
authors: Inoue
authors: Hiroshi
authors: H
authors: Kitamura
authors: Toshiaki
authors: T
authors: Tanaka
authors: Akari
authors: A
authors: Takahashi
authors: Hiroko
authors: H
authors: Asanuma
authors: Naoya
authors: N
authors: Masumori
authors: Taiji
authors: T
authors: Tsukamoto
authors: Noriyuki
authors: N
authors: Sato
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D055786:Gene Knockout Techniques; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met