CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma

H. Okabe, T. Ishimoto, K. Mima, S. Nakagawa, H. Hayashi, H. Kuroki, K. Imai, H. Nitta, S. Saito, D. Hashimoto, A. Chikamoto, T. Ishiko, M. Watanabe, Osamu Nagano, T. Beppu, Hideyuki Saya, H. Baba

Research output: Contribution to journalArticle

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Abstract

Background:Circulating tumour cells (CTCs) have an important role in metastatic processes, but details of their basic characteristics remain elusive. We hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high potential for survival in hepatocellular carcinoma (HCC).Methods:Circulating CD44 + CD90 + cells, previously shown to be tumour-initiating cells, were sorted from human blood and their genetic characteristics were compared with those of tumour cells from primary tissues. The mechanism underlying the high survival potential of CD44-expressing cells in the circulatory system was investigated in vitro.Results:CD44 + CD90 + cells in the blood acquired epithelial-mesenchymal transition, and CD44 expression remarkably increased from the tissue to the blood. In Li7 and HLE cells, the CD44 high population showed higher anoikis resistance and sphere-forming ability than did the CD44 low population. This difference was found to be attributed to the upregulation of Twist1 and Akt signal in the CD44 high population. Twist1 knockdown showed remarkable reduction in anoikis resistance, sphere formation, and Akt signal in HLE cells. In addition, mesenchymal markers and CD44s expression were downregulated in the Twist1 knockdown.Conclusions:CD44s symbolises the acquisition of a mesenchymal phenotype regulating anchorage-independent capacity. CD44s-expressing tumour cells in peripheral blood are clinically important therapeutic targets in HCC.

Original languageEnglish
Pages (from-to)958-966
Number of pages9
JournalBritish Journal of Cancer
Volume110
Issue number4
DOIs
Publication statusPublished - 2014 Feb 18

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Hepatocellular Carcinoma
Cell Survival
Phenotype
Anoikis
Circulating Neoplastic Cells
Population
Epithelial-Mesenchymal Transition
Survival
Neoplastic Stem Cells
Cardiovascular System
Blood Cells
Neoplasms
Up-Regulation
Down-Regulation
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma. / Okabe, H.; Ishimoto, T.; Mima, K.; Nakagawa, S.; Hayashi, H.; Kuroki, H.; Imai, K.; Nitta, H.; Saito, S.; Hashimoto, D.; Chikamoto, A.; Ishiko, T.; Watanabe, M.; Nagano, Osamu; Beppu, T.; Saya, Hideyuki; Baba, H.

In: British Journal of Cancer, Vol. 110, No. 4, 18.02.2014, p. 958-966.

Research output: Contribution to journalArticle

Okabe, H, Ishimoto, T, Mima, K, Nakagawa, S, Hayashi, H, Kuroki, H, Imai, K, Nitta, H, Saito, S, Hashimoto, D, Chikamoto, A, Ishiko, T, Watanabe, M, Nagano, O, Beppu, T, Saya, H & Baba, H 2014, 'CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma', British Journal of Cancer, vol. 110, no. 4, pp. 958-966. https://doi.org/10.1038/bjc.2013.759
Okabe, H. ; Ishimoto, T. ; Mima, K. ; Nakagawa, S. ; Hayashi, H. ; Kuroki, H. ; Imai, K. ; Nitta, H. ; Saito, S. ; Hashimoto, D. ; Chikamoto, A. ; Ishiko, T. ; Watanabe, M. ; Nagano, Osamu ; Beppu, T. ; Saya, Hideyuki ; Baba, H. / CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma. In: British Journal of Cancer. 2014 ; Vol. 110, No. 4. pp. 958-966.
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abstract = "Background:Circulating tumour cells (CTCs) have an important role in metastatic processes, but details of their basic characteristics remain elusive. We hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high potential for survival in hepatocellular carcinoma (HCC).Methods:Circulating CD44 + CD90 + cells, previously shown to be tumour-initiating cells, were sorted from human blood and their genetic characteristics were compared with those of tumour cells from primary tissues. The mechanism underlying the high survival potential of CD44-expressing cells in the circulatory system was investigated in vitro.Results:CD44 + CD90 + cells in the blood acquired epithelial-mesenchymal transition, and CD44 expression remarkably increased from the tissue to the blood. In Li7 and HLE cells, the CD44 high population showed higher anoikis resistance and sphere-forming ability than did the CD44 low population. This difference was found to be attributed to the upregulation of Twist1 and Akt signal in the CD44 high population. Twist1 knockdown showed remarkable reduction in anoikis resistance, sphere formation, and Akt signal in HLE cells. In addition, mesenchymal markers and CD44s expression were downregulated in the Twist1 knockdown.Conclusions:CD44s symbolises the acquisition of a mesenchymal phenotype regulating anchorage-independent capacity. CD44s-expressing tumour cells in peripheral blood are clinically important therapeutic targets in HCC.",
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T1 - CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma

AU - Okabe, H.

AU - Ishimoto, T.

AU - Mima, K.

AU - Nakagawa, S.

AU - Hayashi, H.

AU - Kuroki, H.

AU - Imai, K.

AU - Nitta, H.

AU - Saito, S.

AU - Hashimoto, D.

AU - Chikamoto, A.

AU - Ishiko, T.

AU - Watanabe, M.

AU - Nagano, Osamu

AU - Beppu, T.

AU - Saya, Hideyuki

AU - Baba, H.

PY - 2014/2/18

Y1 - 2014/2/18

N2 - Background:Circulating tumour cells (CTCs) have an important role in metastatic processes, but details of their basic characteristics remain elusive. We hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high potential for survival in hepatocellular carcinoma (HCC).Methods:Circulating CD44 + CD90 + cells, previously shown to be tumour-initiating cells, were sorted from human blood and their genetic characteristics were compared with those of tumour cells from primary tissues. The mechanism underlying the high survival potential of CD44-expressing cells in the circulatory system was investigated in vitro.Results:CD44 + CD90 + cells in the blood acquired epithelial-mesenchymal transition, and CD44 expression remarkably increased from the tissue to the blood. In Li7 and HLE cells, the CD44 high population showed higher anoikis resistance and sphere-forming ability than did the CD44 low population. This difference was found to be attributed to the upregulation of Twist1 and Akt signal in the CD44 high population. Twist1 knockdown showed remarkable reduction in anoikis resistance, sphere formation, and Akt signal in HLE cells. In addition, mesenchymal markers and CD44s expression were downregulated in the Twist1 knockdown.Conclusions:CD44s symbolises the acquisition of a mesenchymal phenotype regulating anchorage-independent capacity. CD44s-expressing tumour cells in peripheral blood are clinically important therapeutic targets in HCC.

AB - Background:Circulating tumour cells (CTCs) have an important role in metastatic processes, but details of their basic characteristics remain elusive. We hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high potential for survival in hepatocellular carcinoma (HCC).Methods:Circulating CD44 + CD90 + cells, previously shown to be tumour-initiating cells, were sorted from human blood and their genetic characteristics were compared with those of tumour cells from primary tissues. The mechanism underlying the high survival potential of CD44-expressing cells in the circulatory system was investigated in vitro.Results:CD44 + CD90 + cells in the blood acquired epithelial-mesenchymal transition, and CD44 expression remarkably increased from the tissue to the blood. In Li7 and HLE cells, the CD44 high population showed higher anoikis resistance and sphere-forming ability than did the CD44 low population. This difference was found to be attributed to the upregulation of Twist1 and Akt signal in the CD44 high population. Twist1 knockdown showed remarkable reduction in anoikis resistance, sphere formation, and Akt signal in HLE cells. In addition, mesenchymal markers and CD44s expression were downregulated in the Twist1 knockdown.Conclusions:CD44s symbolises the acquisition of a mesenchymal phenotype regulating anchorage-independent capacity. CD44s-expressing tumour cells in peripheral blood are clinically important therapeutic targets in HCC.

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