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Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells

BACKGROUND: The important role of cancer stem cells in carcinogenesis has been emphasized in research. CD133+ cells have been mentioned as liver cancer stem cells in hepatocellular carcinoma (HCC). Some researchers have proposed that the sonic hedgehog (Shh) pathway contributes to hepatocarcinogenes...

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Autores principales: Jeng, Kuo-Shyang, Sheen, I-Shyan, Jeng, Wen-Juei, Yu, Ming-Che, Hsiau, Hsin-I, Chang, Fang-Yu, Tsai, Hsin-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741084/
https://www.ncbi.nlm.nih.gov/pubmed/23950652
http://dx.doi.org/10.2147/OTT.S44828
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author Jeng, Kuo-Shyang
Sheen, I-Shyan
Jeng, Wen-Juei
Yu, Ming-Che
Hsiau, Hsin-I
Chang, Fang-Yu
Tsai, Hsin-Hua
author_facet Jeng, Kuo-Shyang
Sheen, I-Shyan
Jeng, Wen-Juei
Yu, Ming-Che
Hsiau, Hsin-I
Chang, Fang-Yu
Tsai, Hsin-Hua
author_sort Jeng, Kuo-Shyang
collection PubMed
description BACKGROUND: The important role of cancer stem cells in carcinogenesis has been emphasized in research. CD133+ cells have been mentioned as liver cancer stem cells in hepatocellular carcinoma (HCC). Some researchers have proposed that the sonic hedgehog (Shh) pathway contributes to hepatocarcinogenesis and that the pathway activation occurs mainly in cancer stem cells. We investigated whether the activation of the Shh pathway occurs in CD133+ cells from liver cancer. MATERIALS AND METHODS: We used magnetic sorting to isolate CD133+ cells from mouse cancer Hepa 1–6 cells. To examine the clonogenicity, cell culture and soft agar colony formation assay were performed between CD133+ and CD133− cells. To study the activation of the Shh pathway, we examined the mRNA expressions of Shh, patched homolog 1 (Ptch-1), glioma-associated oncogene homolog 1 (Gli-1), and smoothened homolog (Smoh) by real-time polymerase chain reaction of both CD133+ and CD133− cells. RESULTS: The number (mean ± standard deviation) of colonies of CD133+ cells and CD133− cells was 1,031.0 ± 104.7 and 119.7 ± 17.6 respectively. This difference was statistically significant (P < 0.001). Their clonogenicity was 13.7% ± 1.4% and 1.6% ± 0.2% respectively with a statistically significant difference found (P < 0.001). CD133+ cells and CD133− cells were found to have statistically significant differences in Shh mRNA and Smoh mRNA (P = 0.005 and P = 0.043 respectively). CONCLUSION: CD133+ Hepa 1–6 cells have a significantly higher colony proliferation and clonogenicity. The Shh pathway is activated in these cells that harbor stem cell features, with an underexpression of Shh mRNA and an overexpression of Smoh mRNA. Blockade of the Shh signaling pathway may be a potential therapeutic strategy for hepatocarcinogenesis.
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spelling pubmed-37410842013-08-15 Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells Jeng, Kuo-Shyang Sheen, I-Shyan Jeng, Wen-Juei Yu, Ming-Che Hsiau, Hsin-I Chang, Fang-Yu Tsai, Hsin-Hua Onco Targets Ther Original Research BACKGROUND: The important role of cancer stem cells in carcinogenesis has been emphasized in research. CD133+ cells have been mentioned as liver cancer stem cells in hepatocellular carcinoma (HCC). Some researchers have proposed that the sonic hedgehog (Shh) pathway contributes to hepatocarcinogenesis and that the pathway activation occurs mainly in cancer stem cells. We investigated whether the activation of the Shh pathway occurs in CD133+ cells from liver cancer. MATERIALS AND METHODS: We used magnetic sorting to isolate CD133+ cells from mouse cancer Hepa 1–6 cells. To examine the clonogenicity, cell culture and soft agar colony formation assay were performed between CD133+ and CD133− cells. To study the activation of the Shh pathway, we examined the mRNA expressions of Shh, patched homolog 1 (Ptch-1), glioma-associated oncogene homolog 1 (Gli-1), and smoothened homolog (Smoh) by real-time polymerase chain reaction of both CD133+ and CD133− cells. RESULTS: The number (mean ± standard deviation) of colonies of CD133+ cells and CD133− cells was 1,031.0 ± 104.7 and 119.7 ± 17.6 respectively. This difference was statistically significant (P < 0.001). Their clonogenicity was 13.7% ± 1.4% and 1.6% ± 0.2% respectively with a statistically significant difference found (P < 0.001). CD133+ cells and CD133− cells were found to have statistically significant differences in Shh mRNA and Smoh mRNA (P = 0.005 and P = 0.043 respectively). CONCLUSION: CD133+ Hepa 1–6 cells have a significantly higher colony proliferation and clonogenicity. The Shh pathway is activated in these cells that harbor stem cell features, with an underexpression of Shh mRNA and an overexpression of Smoh mRNA. Blockade of the Shh signaling pathway may be a potential therapeutic strategy for hepatocarcinogenesis. Dove Medical Press 2013-08-05 /pmc/articles/PMC3741084/ /pubmed/23950652 http://dx.doi.org/10.2147/OTT.S44828 Text en © 2013 Jeng et al, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Jeng, Kuo-Shyang
Sheen, I-Shyan
Jeng, Wen-Juei
Yu, Ming-Che
Hsiau, Hsin-I
Chang, Fang-Yu
Tsai, Hsin-Hua
Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells
title Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells
title_full Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells
title_fullStr Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells
title_full_unstemmed Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells
title_short Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells
title_sort activation of the sonic hedgehog signaling pathway occurs in the cd133 positive cells of mouse liver cancer hepa 1–6 cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741084/
https://www.ncbi.nlm.nih.gov/pubmed/23950652
http://dx.doi.org/10.2147/OTT.S44828
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