CD44 as a cancer stem cell marker and its prognostic value in patients with ovarian carcinoma

Bartáková, Alena; Michalova, Kveta; Presl, J; Vlasák, Pavel; Kosťun, Ján; Bouda, J

doi:10.1080/01443615.2017.1336753

Cited by 30 publications

(23 citation statements)

References 18 publications

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“…Slug and snail are zinc finger transcription factors that regulate EMT in primary human cancers including pancreatic cancer, breast cancer, gastric cancer, lung cancer, and ovarian cancer [25][26][27] . Cell surface receptor CD44 and urokinase receptor CD87 can be candidate stem cell markers for multiple solid tumors including breast cancer, head and neck cancer, and ovarian cancer [28][29][30][31] . Although CD44 was analyzed to have 26 stemness signature, we could not find CD87 as a stemness marker from the StemChecker 32 .…”

Section: Discussionmentioning

confidence: 99%

TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer

Kim

Ahn

Kang

et al. 2020

Sci Rep

140

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Transforming growth factor-β (TGF-β) promotes tumor invasion and metastasis by inducing epithelialmesenchymal transition (EMT). EMT is often related with acquisition of stemness characteristics. The objective of this study was to determine whether EMT and stemness characteristics induced by TGF-β might be associated with epigenetic regulation in lung cancer. A human normal lung epithelial cell line and four lung cancer cell lines were treated with TGF-β. Transcriptome analysis of BEAS-2B and A549 cells incubated with TGF-β were analyzed through next-generation sequencing (NGS). Western blotting was carried out to investigate expression levels of epithelial and mesenchymal markers. Wound healing and Matrigel invasion assay, sphere formation assay, and in vivo mice tumor model were performed to evaluate functional characteristics of EMT and stemness acquisition. To investigate whether activation of EMT and stem cell markers might be involved in epigenetic regulation of lung cancer, experiment using a DNA methyltransferase inhibitor (5-azacytidine, AZA), methylationspecific PCR (MSP) and bisulfite sequencing were performed. NGS revealed changes in expression levels of EMT markers (E-cadherin, N-cadherin, fibronectin, vimentin, slug and snail) and stem cell markers (CD44 and CD87) in both BEAS-2B and A549 cells. Functional analysis revealed increased migration, invasion, sphere formation, and tumor development in mice after TGF-β treatment. Expression of slug and CD87 genes was activated following treatment with AZA and TGF-β. MSP and bisulfite sequencing indicated DNA demethylation of slug and CD87 genes. These results suggest that TGF-β induced EMT and cancer stemness acquisition could be associated with activation of slug and CD87 gene by their promoter demethylation. Although improvements have been made in cancer treatment, lung cancer remains the leading cause of cancer death worldwide. The poor prognosis is due to its diagnosis at advanced stage of the disease 1,2. Failure in treatment is related with cancer recurrence and metastasis. It has been reported that both epithelial-mesenchymal transition (EMT) and acquisition of cancer stemness play important roles in the invasion, metastasis, and chemoresistance of solid tumors 3,4. Transforming growth factor-beta (TGF-β) regulates invasion and metastasis through loss of epithelial markers and gain of mesenchymal markers. TGF-β induced EMT is a major feature of EMT invasiveness and metastasis

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Section: Discussionmentioning

confidence: 99%

TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer

Kim

Ahn

Kang

et al. 2020

Sci Rep

140

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“…CSCs share some common surface markers with normal stem cells, such as CD133, CD44, and CD99. 51 , 52 ESC nuclear transcription factors such as SOX-2, Oct3/4, Klf-4, Nanog, and c-Myc are also regarded as CSC markers. 53 – 55 One study showed that even Nestin, a specific marker of neural stem cells, can be used to identify CSCs.…”

Section: Tumor Inflammatory Microenvironmentmentioning

confidence: 99%

Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial–mesenchymal transition

Chen¹,

Tan²,

Wang³

2018

OTT

101

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Cancer stem cells are a small population of cells with the potential for self-renewal and multi-directional differentiation and are an important source of cancer initiation, treatment resistance, and recurrence. Epithelial–mesenchymal transition (EMT) is a process in which epithelial cells lose their epithelial phenotype and convert to mesenchymal cells. Recent studies have shown that cancer cells undergoing EMT can become stem-like cells. Many kinds of tumors are associated with chronic inflammation, which plays a role in tumor progression. Among the various immune cells mediating chronic inflammation, macrophages account for ~30%–50% of the tumor mass. Macrophages are highly infiltrative in the tumor microenvironment and secrete a series of inflammatory factors and cytokines, such as transforming growth factor (TGF)-β, IL-6, IL-10, and tumor necrosis factor (TNF)-α, which promote EMT and enhance the stemness of cancer cells. This review summarizes and discusses recent research findings on some specific mechanisms of tumor-associated macrophage-derived cytokines in EMT and cancer stemness transition, which are emerging targets of cancer treatment.

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“…One found that 17 biomarkers had been reported in other cancers, including ANXA2, TACSTD2, TNFSF10, HNRNPA2B1, RBP4, PPP1R13L, UGT8, VTN, BCAT1, PTPN2, PDIA6, MFAP4, GSTZ1, NUCB2, P4HB and PTBP1, which indicated our new found biomarkers were reliable. Numerous reported EOC protein biomarkers such as MUC16, MSLN, ERBB2, CHI3L1, MUC1, CD44, VTCN1 and CRP (Simon et al 2007, Chiang et al 2015, Stewart et al 2015, Jiang et al 2017, Bartakova et al 2018, Fortner et al 2018 were also identified in this iTRAQ proteomics study. It demonstrated that iTRAQ proteomic strategy is a reliable tool for identity of EOC biomarker.…”

Section: Discussionmentioning

confidence: 57%

“…For example, VTCN1 was overexpressed in early-stage EOCs and was independent of CA125 expression (Simon et al 2007, Fortner et al 2018 and CDKN2A was the similar biomarker for early-stage EOCs (Jiang et al 2017). CD44, PLAT and PTBP1 showed prognostic value in EOC patients (Borgfeldt et al 2003, Zhang et al 2010, Bartakova et al 2018. Correlation between tumor mesothelin (MSLN) expression and serum MSLN in EOC patients was fine (Hanaoka et al 2017).…”

Section: Go Enrichment Analysismentioning

confidence: 99%

Quantitative analysis of the mitochondrial proteome in human ovarian carcinomas

Cao

et al. 2018

Endocrine-Related Cancer

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Mitochondria play important roles in growth, signal transduction, division, tumorigenesis and energy metabolism in epithelial ovarian carcinomas (EOCs) without an effective biomarker. To investigate the proteomic profile of EOC mitochondrial proteins, a 6-plex isobaric tag for relative and absolute quantification (iTRAQ) proteomics was used to identify mitochondrial expressed proteins (mtEPs) in EOCs relative to controls, followed by an integrative analysis of the identified mtEPs and the Cancer Genome Atlas (TCGA) data from 419 patients. A total of 5115 quantified proteins were identified from purified mitochondrial samples, and 262 proteins were significantly related to overall survival in EOC patients. Furthermore, 63 proteins were identified as potential biomarkers for the development of an EOC, and our findings were consistent with previous reports on a certain extent. Pathway network analysis identified 70 signaling pathways. Interestingly, the results demonstrated that cancer cells exhibited an increased dependence on mitophagy, such as peroxisome, phagosome, lysosome, valine, leucine and isoleucine degradation and fatty acid degradation pathways, which might play an important role in EOC invasion and metastasis. Five proteins (GLDC, PCK2, IDH2, CPT2 and HMGCS2) located in the mitochondrion and enriched pathways were selected for further analysis in an EOC cell line and tissues, and the results confirmed reliability of iTRAQ proteomics. These findings provide a large-scale mitochondrial proteomic profiling with quantitative information, a certain number of potential protein biomarkers and a novel vision in the mitophagy bio-mechanism of a human ovarian carcinoma.

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CD44 as a cancer stem cell marker and its prognostic value in patients with ovarian carcinoma

Cited by 30 publications

References 18 publications

TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer

TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer

Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial–mesenchymal transition

Quantitative analysis of the mitochondrial proteome in human ovarian carcinomas

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CD44 as a cancer stem cell marker and its prognostic value in patients with ovarian carcinoma

Cited by 30 publications

References 18 publications

TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer

TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer

Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial&ndash;mesenchymal transition

Quantitative analysis of the mitochondrial proteome in human ovarian carcinomas

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Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial–mesenchymal transition