Clonal analysis revealed functional heterogeneity in cancer stem-like cell phenotypes in uterine endometrioid adenocarcinoma

Uterine endometrial carcinoma is one of the common cancers in females. Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are a small subpopulation of cancer cells that are tumorigenic and are resistant to treatments, thus they are focused as treatment targets. However, the heterogeneity o...

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Bibliographic Details
Published in:Experimental and molecular pathology 2019-02, Vol.106, p.78-88
Main Authors: Tabuchi, Yuta, Hirohashi, Yoshihiko, Hashimoto, Shinichi, Mariya, Tasuku, Asano, Takuya, Ikeo, Kazuho, Kuroda, Takafumi, Mizuuchi, Masahito, Murai, Aiko, Uno, Sei, Kawai, Noriko, Kubo, Terufumi, Nakatsugawa, Munehide, Kanaseki, Takayuki, Tsukahara, Tomohide, Saito, Tsuyoshi, Torigoe, Toshihiko
Format: Article
Language:English
Subjects:
Cancer stem cell
Chemo-resistance
Endometrial carcinoma
SAGE-Seq
Tumorigenicity
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Summary:Uterine endometrial carcinoma is one of the common cancers in females. Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are a small subpopulation of cancer cells that are tumorigenic and are resistant to treatments, thus they are focused as treatment targets. However, the heterogeneity of CSCs/CICs is still elusive, and we therefore analyzed CSCs/CICs at the clonal level. We previously established sphere-cultured CSCs/CICs from primary human uterine endometrial carcinoma, and we isolated several clones from CSCs/CICs in this study. Interestingly, we established two types of clones based on the growth pattern. The clones were termed sphere clones (S clones) and leukemia-like clones (LL clones). Functional analysis revealed that S clones are resistant to chemotherapy, whereas LL clones are sensitive to chemotherapy. On the other hand, S clones are less tumorigenic, while LL clones are highly tumorigenic. Transcriptome analysis using serial analysis of gene expression sequencing (SAGE-Seq) revealed distinctive gene expression profiles in S clone cells and LL clone cells. The results indicate that CSCs/CICs are composed of functionally heterogenic subpopulations including highly tumorigenic clones and treatment-resistant clones and that the characteristics of CSCs/CICs might be determined by the characteristics of different clones that compose CSCs/CICs.
ISSN:0014-4800
1096-0945
DOI:10.1016/j.yexmp.2018.11.013