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cd133 and membrane microdomains:Old facets for future hypotheses

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World Journal of Gastroenterology 2011年第36期17卷 4149-4152页

作者： Christine A Fargeas Jana Karbanová József Jászai Denis Corbeil Tissue Engineering Laboratories (BIOTEC) Technische Universitt DresdenD-01307 DresdenGermany

Understanding all facets of membrane microdomains in normal and cancerous cells within the digestive tract is highly important,not only from a clinical point of view,but also in terms of our basic knowledge of cellular *** studying the normal and cancer stem cell-associated molecule cd133 (prominin-1),novel aspects of the organization and dynamics of polarized epithelial cells have been revealed during the last *** association with particular membrane microdomains is highly relevant in these contexts and might also offer new avenues in diagnosis and/or targeting of cancer stem cells.

关键词： AC133 Cancer cd133 Membrane microdomains Membrane vesicles Prominin-1 Stem cell

cd133:A cancer stem cells marker, is used in colorectal cancers

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World Journal of Gastroenterology 2013年第17期19卷 2603-2611页

作者： Fei Ren Wei-Qi Sheng Xiang Du Department of Pathology Shanghai Cancer Center Fudan University

Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and selfrenewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as cd133, have been of great interest. cd133, a five-transmembrane glycoprotein, is widely used as a marker to identify and isolate colorectal cancer stem cells. This marker has been investigated to better understand the characteristics and functions of cancer stem cells. Moreover, it can also be used to predict tumor progression, patient survival, chemoradiotherapy resistance and other clinical parameters. In this review, we discuss the use of cd133 in the identification of colorectal cancer stem cell, which is currently controversial. Although the function of cd133 is as yet unclear, we have discussed several possible functions and associated mechanisms that may partially explain the role of cd133 in colorectal cancers. In addition, we focus on the prognostic value of cd133 in colorectal cancers. Finally, we predict that cd133 may be used as a possible target for colorectal cancer treatment.

关键词： cd133 Colorectal cancer Cancer stem cells Prognosis Chemoradiotherapy resistance

Autologous cd34^+ and cd133^+ stem cells transplantation in patients with end stage liver disease

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World Journal of Gastroenterology 2010年第42期16卷 5297-5305页

作者： Hosny Salama Abdel-Rahman N Zekri Abeer A Bahnassy Eman Medhat Hanan A Halim Ola S Ahmed Ghada Mohamed Sheren A Al Alim Ghada M Sherif Tropical Medicine Department El-Kasr Al-Aini School of MedicineKasr Al-Aini st.Kasr AlAini11977 CairoEgypt Virology and Immunology Unit Cancer Biology DepartmentNational Cancer InstituteCairo UniversityKasr Al-Aini st.Fom El-Khaleeg11976 CairoEgypt Pathology Department National Cancer InstituteCairo UniversityKasr Al-Aini st.Fom El-Khaleg11976 CairoEgypt Biostatistics and Epidemiology Department National Cancer InstituteCairo University11976 CairoEgypt

AIM:To assess the utility of an autologous cd34 + and cd133 + stem cells infusion as a possible therapeutic modality in patients with end-stage liver ***:One hundred and forty patients with endstage liver diseases were randomized into two *** 1,comprising 90 patients,received granulocyte colony stimulating factor for five days followed by autologous cd34 + and cd133 + stem cell infusion in the portal *** 2,comprising 50 patients,received regular liver treatment only and served as a control ***:Near normalization of liver enzymes and improvement in synthetic function were observed in 54.5% of the group 1 patients;13.6% of the patients showed stable states in the infused *** of the patients in the control group showed *** adverse effects were ***:Our data showed that a cd34 + and cd133 + stem cells infusion can be used as supportive treatment for end-stage liver disease with satisfactory tolerability.

关键词： cd34 cd133 Stem cell Liver Hepatitis C virus

Inhibitive effect of IL-24 gene on cd133^+ laryngeal cancer cells

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Asian Pacific Journal of Tropical Medicine 2014年第11期7卷 867-872页

作者： Jin-Zhang Cheng Dan Yu Hui Zhang Chun-Shun Jin Yan Liu Xue Zhao Xin-Meng Qi Xueshi-Bojie Liu Second Affiliated Hospital of Jilin University

Objective:To explore the inhihitive and apoptosis inductive effect of IL-24 genes on cd133^+laryngeal cancer cells in Hep-2 ***:Human peripheral blood monocytes were *** total RNA was extracted by using Trizol method and reverse transcripted into cdNA using RT-PCR *** P1 and P2 was designed for the amplification of human IL-24 *** confirmation of agarose gel electrophoresis tests,TA was cloned into pMD19-T simple *** Ⅰ and Xho Ⅰ double digesting human IL-24 and pIRES2-ZsGreen1 and eukaryotic expression vector were used to establish the pIRES2-ZsGreen1-hIL-24 vector,and detected by enzyme digestion and gene sequencing *** cytometry(FCM) was used to isolate cd133^+ cells from Hep-2 ***133^+ cells were transfected with pIRES2-ZsGreen1-hIL-24 through liposome *** detection,MTT and FCM were used to observe the effect of IL-24 gene on cd133^+ laryngeal cancer Hep-2 ***:Lipotin mediated transfection of recombinant pIRES2-ZsGreen1-hIL-24 plasmid into cd133^+ Hep-2 could expressed IL-24 gene in cells *** results showed that IL-24 transfected group was significantly suppressed compared to empty vector group and control group(Pcd133^+laryngeal cells in Hep-2 line and promote their apoptosis.

关键词： IL-24 cd133 Laryngeal cancer Cancer stem cells Gene therapy

Upregulated cd133 expression in tumorigenesis of colon cancer cells

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World Journal of Gastroenterology 2011年第7期17卷 932-937页

作者： Zhi-Li Yang Qi Zheng Jun Yan Ye Pan Zhi-Gang Wang Department of Surgery Affiliated Sixth People's Hospital ofShanghai Jiao Tong University Shanghai 200233 China

AIM: To analyze the upregulated cd133 expression in tumorigenesis of primary colon cancer cells. METHODS: Upregulated cd133 expression in tumorigenesis of colorectal cancer cell lines (Lovo, Colo205, Caco-2, HCT116 and SW620) was analyzed by flow cytometry. Human colon cancer tissue samples were stained with anti-human cd133. SW620 cells were sorted according to the cd133 expression level measured by fluorescence-activated cell sorting. Spheroids of colorectal cancer cells were cultured with the hanging drop. Expression of cd133 and Lgr5 in spheroids of colorectal cancer cells and monolayer culture was detected by RT-qPCR. Spheroids of colorectal cancer cells were analyzed using anti-human cd133 with immunohistochemical staining. RESULTS: cd133 antigen was expressed in colorectal cancer cell lines (Lovo, Colo205, Caco-2, HCT116 and SW620) as well as in primary and metastatic human colon cancer tissues. However, the cd133 was differently expressed in these cell lines and tissues. The expression levels of cd133 and Lgr5 were significantly higher in spheroids of parental, cd133hi and cd133-cells than in their monolayer culture at the mRNA level (P cd133-cells showed that cd133 was highly expressed in colorectal cancer cell lines. CONCLUSION: Upregulated cd133 expression plays a role in tumorigenesis colorectal cancer cells, which may promote the expression of other critical genes that can drive tumorigenesis.

关键词： cd133 Colon cancer cells Tumorigenesis Cancer stem cells

Promoter hypermethylation and loss of cd133 gene expression in colorectal cancers

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World Journal of Gastroenterology 2010年第25期16卷 3153-3160页

作者： You-Kyung Jeon Sung-Hee Kim Seung-Ho Choi Kyung-Hee Kim Byong-Chul Yoo Ja-Lok Ku Jae-Gahb Park Laboratory of Cell Biology Cancer Research Institute Seoul National University College of Medicine Seoul 110-799 South Korea Colorectal Cancer Branch Research Institute National Cancer Center Goyang 411-764 Gyeonggi South Korea

AIM: To understand cd133 promoter hypermethyl-ation and expression in 32 colorectal cancer cell lines. METHODS: Nucleic acid was isolated from 32 colorectal cancer cell lines and cd133 expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. Promoter methylation status of the cd133 gene was analyzed with a methylation-specific PCR after sodium-bisulfi te modification and by clonal sequencing analysis. The correlation between expression and promoter methylation of cd133 gene was confirmed with treatment of 5-aza-2’-deoxycytidine. RESULTS: We measured cd133 expression levels in 32 colorectal cancer cell lines. RT-PCR analysis showed undetectable or low levels of cd133 expression in 34.4%of cell lines. To verify the relation between cd133 expression and methylation status of the cd133 gene promoter in colorectal carcinogenesis, cd133 gene promoter hypermethylation was analyzed in 32 cancer cell lines. Promoter hypermethylation was detected in 13 (40.6%) of the cell lines using methylation specificPCR and confirmed by bisulfite sequencing analysis. Treatment of 11 of the cell lines with the demethylation agent 5-aza-2’-deoxycytidine recovered cd133 expression in most of them. CONCLUSION: Transcriptional repression of cd133 is caused by promoter hypermethylation of the cd133 CpG islands in some of colorectal cancer cell lines. The study may contribute to the understanding of the role of cd133 inactivation in the progression of colorectal cancers.

关键词： cd133 Promoter Hypermethylation Colorectal cancer Sodium bisulfite modification

Angioarchitecture and cd133^+ tumor stem cell distribution in intracranial hemangiopericytoma A comparative study with meningioma

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Neural Regeneration Research 2011年第34期6卷 2687-2693页

作者： Zhongguo Zhang Mingguang Zhao Zaihua Xu Zhenquan Song Department of Neurosurgery Northern Hospital Shenyang 110840 Liaoning Province China Surgical Department of Colorectal Cancer Liaoning Provincial Cancer Hospital Shenyang 110042 Liaoning Province China

Angioarchitecture plays an important role in the malignant development of intracranial hemangiopericytoma. It remains poorly understood whether high frequency of hemorrhage during clinical surgery for intracranial hemangiopericytoma is associated with angioarchitecture. The present study utilized hematoxylin-eosin staining, and immunohistochemical staining with epithelial membrane antigen, vimentin, cd34, von Willebrand factor （vWF） and cd133 to observe characteristics of angioarchitecture. In addition, silver stains were used to demonstrate changes in reticular fibers in the wall of vessel channels in intracranial hemangiopericytoma and meningioma. Five patterns of angioarchitecture were identified in intracranial hemangiopericytoma, namely tumor cell islands, vasculogenic mimicry, mosaic blood vessels, sprouting angiogenesis, and intussusceptive angiogenesis. Several cd133＋ tumor cells were found to form tumor cell islands. A connection between vWF ^＋ and vWF channels was detected in the pattern of intussusceptive angiogenesis, and some vimentin^＋ tumor cells were embedded in the periodic acid-Schiff positive channel wall. Incomplete threads of reticular fibers formed the walls of larger pseudo-vascular channels and some tumor clumps or scattered tumor cells were detected ＂floating＂ in them. The angioarchitecture, specific markers and reticular fibers of intracranial hemangiopericytoma were significantly different from meningioma. Angioarchitecture provides a functional vascular network for vascular evolution in intracranial hemangiopericytoma and contributes to significant intra-operative bleeding.

关键词： intracranial hemangiopericytoma angioarchitecture tumor cell islands vasculogenic mimicry mosaic blood vessels, sprouting angiogenesis intussusceptive angiogenesis meningioma cd133

Cancer stem cell markers cd133 and cd24 correlate with invasiveness and differentiation in colorectal adenocarcinoma

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World Journal of Gastroenterology 2009年第18期15卷 2258-2264页

作者： Dongho Choi Hyo Won Lee Kyung Yul Hur Jae Joon Kim Gyeong-Sin Park Si-Hyong Jang Young Soo Song Ki-Seok Jang Seung Sam Paik Department of Surgery College of MedicineSoonchunhyang University140-743 SeoulSouth Korea Department of Surgery Chi Hang Hospital140-741 SeoulSouth Korea Department of Pathology College of MedicineCatholic University137-040 SeoulSouth Korea Department of Pathology College of MedicineHanyang University133-790 SeoulSouth Korea

AIM:To verify that cd markers are available for detecting cancer stem cell populations and to evaluate their clinical significance in colon ***:Immunohistochemistry for cd133,cd24 and cd44 was performed on the tissue microarray of 523 colorectal *** records were reviewed and clinicopathological analysis was ***:In colorectal adenocarcinoma,128 of 523 cases(24.5%) were positive and 395 cases(75.5%) were negative for cd133 *** hundred and sixty-four of 523 cases(50.5%) were positive and 259 cases(49.5%) were negative for cd24 *** hundred and two of 523 cases(96%) were negative and 21 cases(4%) were positive for cd44 *** clinicopathological analysis,cd133 expression was present more in male patients(P = 0.002) and in advanced T stage cancer(P = 0.024).Correlation between cd24 expression and clinicopathological factors was seen in the degree of differentiation(P = 0.006).Correlation between cd44 expression and clinicopathological factors was seen in the tumor size(P = 0.001).Survival was not significantly related to cd133,cd24 and cd44 ***:cd markers were related to invasiveness and differentiation of colorectal ***,cd expression was not closely related to survival.

关键词： cd133 cd24 cd44 Colon cancer stemcells Colorectal adenocarcinoma

A non-metabolic function of hexokinase 2 in small cell lung cancer:promotes cancer cell stemness by increasing USP11-mediated cd133 stability

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Cancer Communications 2022年第10期42卷 1008-1027页

作者： Juhong Wang Fei Shao Yannan Yang Wei Wang Xueying Yang Renda Li Hong Cheng Sijin Sun Xiaoli Feng Yibo Gao Jie He Zhimin Lu Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Laboratory of Translational Medicine National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Central Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116P.R.China Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhouZhejiang 310029P.R.China Cancer Center Zhejiang UniversityHangzhouZhejiang 310029P.R.China

Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor *** a key glycolytic enzyme,hexokinase 2(HK2)plays an instrumental role in aerobic glycolysis and tumor ***,whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer(SCLC)is largely *** this study,we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in ***:Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated ***-like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse *** and mass spectrometry analyses were performed to identify the binding proteins of *** expression levels of cd133-associated and CSC-relevant proteins were evaluated by immunoblotting,immunoprecipitation,immunofluorescence,and immunohistochemistry *** expression levels of Nanog,POU5F1,Lin28,HK2,Prominin-1 were analyzed through quantitative reverse transcription *** of cd133 was examined by in vitro or in vivo ubiquitination ***133+cells were sorted by flow cytometry using an anti-cd133 ***:We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated ***2 depletion inhibited CSC stemness and promoted CSC ***,nonmitochondrial HK2 directly interacted with cd133 and enhanced cd133 expression without affecting cd133 mRNA *** interaction of HK2 and cd133 promoted the binding of the deubiquitinase ubiquitin-specific protease 11(USP11)to cd133,thereby inhibiting cd133 polyubiquitylation and ***2-mediated upregulation of cd133 expression enhanced the expression of cell rene

关键词： HK2 metabolic enzyme non-metabolic function cancer stem-like cell cd133 USP11 ubiquitylation SCLC