https://scholars.lib.ntu.edu.tw/handle/123456789/550947
標題: | Characteristics of CD133-Sustained Chemoresistant Cancer Stem-Like Cells in Human Ovarian Carcinoma | 作者: | Liu, Chao Lien Chen, Ying Jen Fan, Ming Huei Liao, Yi Jen TSUI-LIEN MAO |
關鍵字: | CD133; cancer stem cell (CSC); chemoresistance; ovarian cancer (OC); sphere-forming assay | 公開日期: | 4-九月-2020 | 出版社: | MDPI | 卷: | 21 | 期: | 18 | 來源出版物: | International journal of molecular sciences | 摘要: | Cancer stem cells (CSCs) are considered to be the origin of ovarian cancer (OC) development, recurrence, and chemoresistance. We investigated changes in expression levels of the CSC biomarker, cluster of differentiation 133 (CD133), from primary OC cell lines to induction of CSC-spheres in an attempt to explore the mechanisms related to modulation of stemness, drug resistance, and tumorigenesis in CSCs, thus facilitating the search for new therapeutics for OC. The effect of CD133 overexpression on the induction of CSC properties was evaluated by sphere-forming assays, RT-qPCR, flow cytometry, cell viability assays, and in vivo xenograft experiments. Moreover, the potential signaling molecules that participate in CD133 maintenance of stemness were screened by RNA-sequencing. CD133 expression was upregulated during OCSC induction and chemotherapeutic drug treatment over time, which increased the expressions of stemness-related markers (SOX2, OCT4, and Nanog). CD133 overexpression also promoted tumorigenesis in NOD/SCID mice. Several signalings were controlled by CD133 spheres, including extracellular matrix receptor interactions, chemokine signaling, and Wnt signaling, all of which promote cell survival and cell cycle progression. Our findings suggest that CD133 possesses the ability to maintain functional stemness and tumorigenesis of OCSCs by promoting cell survival signaling and may serve as a potential target for stem cell-targeted therapy of OC. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/550947 | ISSN: | 16616596 | DOI: | 10.3390/ijms21186467 | SDG/關鍵字: | alpha6 integrin; ARID1A protein; beta8 integrin; CD133 antigen; chemokine receptor; cisplatin; cyclic AMP dependent protein kinase; cyclic AMP responsive element binding protein binding protein; Fas ligand; focal adhesion kinase; G protein coupled receptor; Hermes antigen; immunoglobulin G; Ki 67 antigen; low density lipoprotein receptor related protein 5; lymphoid enhancer factor 1; octamer transcription factor 4; paclitaxel; phosphatidylinositol 3 kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein bcl 2; protein kinase B; protein p130; protein p53; T cell factor protein; transcription factor FKHRL1; transcription factor NANOG; transcription factor Sox2; unclassified drug; CD133 antigen; PROM1 protein, human; animal cell; animal experiment; animal model; animal tissue; Article; body weight; cancer stem cell; carcinogenesis; cell cycle arrest; cell cycle progression; cell proliferation; cell viability; controlled study; drug-resistant cell line; extracellular matrix; flow cytometry; gene expression; gene mutation; gene overexpression; genotype phenotype correlation; high throughput sequencing; HTB75 cell line; human; human cell; IC50; IGROV-1 cell line; immunofluorescence; immunohistochemistry; in vivo study; microscopy; mouse; MTT assay; nonhuman; ovarian carcinoma cell line; OVCAR-3 cell line; progression free survival; reverse transcription polymerase chain reaction; RNA extraction; RNA sequencing; short tandem repeat; signal transduction; SK-OV-3 cell line; sphere forming assay; stemness; tumor growth; Western blotting; Wnt signaling; animal; cancer stem cell; carcinoma; cell differentiation; drug resistance; female; gene expression regulation; genetics; metabolism; nonobese diabetic mouse; organoid; ovary tumor; pathology; physiology; SCID mouse; tumor cell line; xenograft; AC133 Antigen; Animals; Carcinogenesis; Carcinoma; Carcinoma, Ovarian Epithelial; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Neoplastic Stem Cells; Organoids; Ovarian Neoplasms; Signal Transduction |
顯示於: | 病理學科所 |
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