CD133 Expression in the Nucleus Is Associated with Endometrial Carcinoma Staging and Tumor Angioinvasion

Pietrus, Miłosz; Pityński, Kazimierz; Waligóra, Marcin; Milian-Ciesielska, Katarzyna; Bialon, Monika; Ludwin, Artur; Skrzypek, Klaudia

doi:10.3390/jcm10102144

Cited by 6 publications

(12 citation statements)

References 35 publications

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“…Although there is a lack of consensus on the cell surface markers for human uterine stem cells, it is intriguing to point out that several groups have reported cell surface markers CD133 and ALDH-1 in side population enriched from human endometrial cancer tissues [ 32 – 34 ]. These markers are indeed specific for VSELs [ 35 , 36 ] and although there is no report on VSELs in normal human uterine tissue, consensus seems to exist in stem cells markers in endometrial cancer possibly because of increased numbers of OCT-4 positive stem/progenitor cells in disease state.…”

Section: Discussionmentioning

confidence: 99%

Additional evidence to support OCT-4 positive VSELs and EnSCs as the elusive tissue-resident stem/progenitor cells in adult mice uterus

2022

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Objective True identity and specific set of markers to enrich endometrial stem cells still remains elusive. Present study was undertaken to further substantiate that very small embryonic-like stem cells (VSELs) are the true and elusive stem cells in adult mice endometrium. Methods This was achieved by undertaking three sets of experiments. Firstly, SSEA-1+ and Oct-4 + positive VSELs, sorted from GFP mice, were transplanted into the uterine horns of wild-type Swiss mice and GFP uptake was studied within the same estrus cycle. Secondly, uterine lumen was scratched surgically and OCT-4 expressing stem/progenitor cells were studied at the site of injury after 24–72 h. Thirdly, OCT-4 expression was studied in the endometrium and myometrium of adult mice after neonatal exposure to estradiol (20 µg/pup/day on days 5–7 after birth). Results GFP + ve VSELs expressing SSEA-1 and Oct-4 engrafted and differentiated into the epithelial cells lining the lumen as well as the glands during the estrus stage when maximum remodeling occurs. Mechanical scratching activated tissue-resident, nuclear OCT-4 positive VSELs and slightly bigger ‘progenitors’ endometrial stem cells (EnSCs, cytoplasmic OCT-4) which underwent clonal expansion and further differentiated into luminal and glandular epithelial cells. Neonatal exposure to endocrine disruption resulted in increased numbers of OCT-4 positive VSELs/EnSCs in adult endometrium. Discussion Results support the presence of functionally active VSELs in adult endometrium. VSELs self-renew and give rise to EnSCs that further differentiate into epithelial cells under normal physiological conditions. Also, VSELs are vulnerable to endocrine insults. To conclude VSELs are true and elusive uterine stem cells that maintain life-long uterine homeostasis and their dysregulation may result in various pathologies. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Additional evidence to support OCT-4 positive VSELs and EnSCs as the elusive tissue-resident stem/progenitor cells in adult mice uterus

2022

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“…They performed an immunohistochemical study of CD133 expression in the plasma membrane, nucleus, and cytoplasm in a group of 64 patients with endometrial cancer and found that CD133 nuclear expression is directly associated with the stage of disease. Specifically, CD133 nuclear expression was increased in stages IB-IV compared to stage IA [11]. In hepatocellular carcinoma patients, nuclear CD133 expression was an indicator of poor prognosis: median survival span 12 months versus 34.5 months for patients with no nuclear CD133 expression [195].…”

Section: Subcellular Localization Of Cd133 May Vary At Different Stag...mentioning

confidence: 94%

“…It has been established that the CD133 glycoprotein on the plasma membrane resides in specialized lipid microdomains rich in cholesterol and sphingolipids, i.e., lipid rafts [8]. Recent studies have also revealed nuclear localization of CD133 [9][10][11]. Figure 1B shows all sites of the CD133 cellular localization.…”

Section: Introductionmentioning

confidence: 94%

“…Moreover, it was found that high nuclear CD133 expression and high cytoplasmic CD133 expression were prognostic factors for poor outcome of non-small cell lung cancer [49]. Pietrus et al investigated the association of subcellular expression of CD133 with the clinical manifestations and outcomes of the endometrial cancer [11]. They performed an immunohistochemical study of CD133 expression in the plasma membrane, nucleus, and cytoplasm in a group of 64 patients with endometrial cancer and found that CD133 nuclear expression is directly associated with the stage of disease.…”

Section: Subcellular Localization Of Cd133 May Vary At Different Stag...mentioning

confidence: 99%

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Can CD133 Be Regarded as a Prognostic Biomarker in Oncology: Pros and Cons

Gisina,

Kim,

Yarygin

et al. 2023

IJMS

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The CD133 cell membrane glycoprotein, also termed prominin-1, is expressed on some of the tumor cells of both solid and blood malignancies. The CD133-positive tumor cells were shown to exhibit higher proliferative activity, greater chemo- and radioresistance, and enhanced tumorigenicity compared to their CD133-negative counterparts. For this reason, CD133 is regarded as a potential prognostic biomarker in oncology. The CD133-positive cells are related to the cancer stem cell subpopulation in many types of cancer. Recent studies demonstrated the involvement of CD133 in the regulation of proliferation, autophagy, and apoptosis in cancer cells. There is also evidence of its participation in the epithelial–mesenchymal transition associated with tumor progression. For a number of malignant tumor types, high CD133 expression is associated with poor prognosis, and the prognostic significance of CD133 has been confirmed in a number of meta-analyses. However, some published papers suggest that CD133 has no prognostic significance or even demonstrate a certain correlation between high CD133 levels and a positive prognosis. This review summarizes and discusses the existing evidence for and against the prognostic significance of CD133 in cancer. We also consider possible reasons for conflicting findings from the studies of the clinical significance of CD133.

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“…While CA125 is known as a biomarker for ovarian cancer [45], its utility for endometrial cancer is uncertain [46]. Increased SLC26A2 expression distinguishes endometrioid from serous carcinoma [47], and the association of PROM1 with poorer prognosis indicates its potential as a biomarker for identifying high-risk patients [48].…”

Section: Ev-based Histological Subtype Biomarkersmentioning

confidence: 99%

The tumour‐derived extracellular vesicle proteome varies by endometrial cancer histology and is confounded by an obesogenic environment

Artuyants,

Guo,

Flinterman

et al. 2024

Proteomics

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Endometrial cancer, the most common gynaecological cancer worldwide, is closely linked to obesity and metabolic diseases, particularly in younger women. New circulating biomarkers have the potential to improve diagnosis and treatment selections, which could significantly improve outcomes. Our approach focuses on extracellular vesicle (EV) biomarker discovery by directly profiling the proteome of EVs enriched from frozen biobanked endometrial tumours. We analysed nine tissue samples to compare three clinical subgroups—low BMI (Body Mass Index) Endometrioid, high BMI Endometrioid, and Serous (any BMI)—identifying proteins related to histological subtype, BMI, and shared secreted proteins. Using collagenase digestion and size exclusion chromatography, we successfully enriched generous quantities of EVs (range 204.8–1291.0 µg protein: 1.38 × 1011–1.10 × 1012 particles), characterised by their size (∼150 nm), expression of EV markers (CD63/81), and proposed endometrial cancer markers (L1CAM, ANXA2). Mass spectrometry‐based proteomic profiling identified 2075 proteins present in at least one of the 18 samples. Compared to cell lysates, EVs were successfully depleted for mitochondrial and blood proteins and enriched for common EV markers and large secreted proteins. Further analysis highlighted significant differences in EV protein profiles between the high BMI subgroup and others, underlining the impact of comorbidities on the EV secretome. Interestingly, proteins differentially abundant in tissue subgroups were largely not also differential in matched EVs. This research identified secreted proteins known to be involved in endometrial cancer pathophysiology and proposed novel diagnostic biomarkers (EIF6, MUC16, PROM1, SLC26A2).

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CD133 Expression in the Nucleus Is Associated with Endometrial Carcinoma Staging and Tumor Angioinvasion

Cited by 6 publications

References 35 publications

Additional evidence to support OCT-4 positive VSELs and EnSCs as the elusive tissue-resident stem/progenitor cells in adult mice uterus

Additional evidence to support OCT-4 positive VSELs and EnSCs as the elusive tissue-resident stem/progenitor cells in adult mice uterus

Can CD133 Be Regarded as a Prognostic Biomarker in Oncology: Pros and Cons

The tumour‐derived extracellular vesicle proteome varies by endometrial cancer histology and is confounded by an obesogenic environment

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