High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.

Epithelioid sarcoma (ES) is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we...

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Autores principales: Makoto Emori, Tomohide Tsukahara, Masaki Murase, Masanobu Kano, Kenji Murata, Akari Takahashi, Terufumi Kubo, Hiroko Asanuma, Kazuyo Yasuda, Vitaly Kochin, Mitsunori Kaya, Satoshi Nagoya, Jun Nishio, Hiroshi Iwasaki, Tomoko Sonoda, Tadashi Hasegawa, Toshihiko Torigoe, Takuro Wada, Toshihiko Yamashita, Noriyuki Sato
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:285cbb14125e4ee48aa2b023a1193d052021-11-18T08:40:49ZHigh expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.1932-620310.1371/journal.pone.0084187https://doaj.org/article/285cbb14125e4ee48aa2b023a1193d052013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376795/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Epithelioid sarcoma (ES) is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX) and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs) based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high) cells) correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high) cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009). In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.Makoto EmoriTomohide TsukaharaMasaki MuraseMasanobu KanoKenji MurataAkari TakahashiTerufumi KuboHiroko AsanumaKazuyo YasudaVitaly KochinMitsunori KayaSatoshi NagoyaJun NishioHiroshi IwasakiTomoko SonodaTadashi HasegawaToshihiko TorigoeTakuro WadaToshihiko YamashitaNoriyuki SatoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84187 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Makoto Emori
Tomohide Tsukahara
Masaki Murase
Masanobu Kano
Kenji Murata
Akari Takahashi
Terufumi Kubo
Hiroko Asanuma
Kazuyo Yasuda
Vitaly Kochin
Mitsunori Kaya
Satoshi Nagoya
Jun Nishio
Hiroshi Iwasaki
Tomoko Sonoda
Tadashi Hasegawa
Toshihiko Torigoe
Takuro Wada
Toshihiko Yamashita
Noriyuki Sato
High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.
description Epithelioid sarcoma (ES) is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX) and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs) based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high) cells) correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high) cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009). In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.
format article
author Makoto Emori
Tomohide Tsukahara
Masaki Murase
Masanobu Kano
Kenji Murata
Akari Takahashi
Terufumi Kubo
Hiroko Asanuma
Kazuyo Yasuda
Vitaly Kochin
Mitsunori Kaya
Satoshi Nagoya
Jun Nishio
Hiroshi Iwasaki
Tomoko Sonoda
Tadashi Hasegawa
Toshihiko Torigoe
Takuro Wada
Toshihiko Yamashita
Noriyuki Sato
author_facet Makoto Emori
Tomohide Tsukahara
Masaki Murase
Masanobu Kano
Kenji Murata
Akari Takahashi
Terufumi Kubo
Hiroko Asanuma
Kazuyo Yasuda
Vitaly Kochin
Mitsunori Kaya
Satoshi Nagoya
Jun Nishio
Hiroshi Iwasaki
Tomoko Sonoda
Tadashi Hasegawa
Toshihiko Torigoe
Takuro Wada
Toshihiko Yamashita
Noriyuki Sato
author_sort Makoto Emori
title High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.
title_short High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.
title_full High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.
title_fullStr High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.
title_full_unstemmed High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.
title_sort high expression of cd109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line esx and is related to poor prognosis of soft tissue sarcoma.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/285cbb14125e4ee48aa2b023a1193d05
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