Journal
CANCER SCIENCE
Volume 104, Issue 4, Pages 431-436Publisher
WILEY
DOI: 10.1111/cas.12104
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Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [16209013, 17016061, 15659097, 24592399]
- Ministry of Health, Labor and Welfare of Japan [15-17, 19-14]
- Ono Cancer Research Fund
- Takeda Science Foundation
- National Cancer Center Research and Development Fund [23-A-44]
- Grants-in-Aid for Scientific Research [24590449, 24791467, 24659165, 24592399, 221S0001] Funding Source: KAKEN
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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 (ALDH1high) cells using the ALDEFLUOR assay; however, the molecular mechanisms of prostate CSCs/CICs are still elusive. Prostate CSCs/CICs were isolated as ALDH1high 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. (Cancer Sci 2013; 104: 431-436)
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