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Fu X, He Q, Tao Y, Wang M, Wang W, Wang Y, Yu QC, Zhang F, Zhang X, Chen YG, Gao D, Hu P, Hui L, Wang X, Zeng YA. Recent advances in tissue stem cells. SCIENCE CHINA. LIFE SCIENCES 2021; 64:1998-2029. [PMID: 34865207 DOI: 10.1007/s11427-021-2007-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 06/08/2021] [Indexed: 12/13/2022]
Abstract
Stem cells are undifferentiated cells capable of self-renewal and differentiation, giving rise to specialized functional cells. Stem cells are of pivotal importance for organ and tissue development, homeostasis, and injury and disease repair. Tissue-specific stem cells are a rare population residing in specific tissues and present powerful potential for regeneration when required. They are usually named based on the resident tissue, such as hematopoietic stem cells and germline stem cells. This review discusses the recent advances in stem cells of various tissues, including neural stem cells, muscle stem cells, liver progenitors, pancreatic islet stem/progenitor cells, intestinal stem cells, and prostate stem cells, and the future perspectives for tissue stem cell research.
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Affiliation(s)
- Xin Fu
- Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200233, China
| | - Qiang He
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Yu Tao
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Mengdi Wang
- State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Wei Wang
- State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yalong Wang
- The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China
| | - Qing Cissy Yu
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Fang Zhang
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Xiaoyu Zhang
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Ye-Guang Chen
- The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
- Max-Planck Center for Tissue Stem Cell Research and Regenerative Medicine, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510530, China.
| | - Dong Gao
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
| | - Ping Hu
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200233, China.
- Max-Planck Center for Tissue Stem Cell Research and Regenerative Medicine, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510530, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Bio-Research Innovation Center, Shanghai Institute of Biochemistry and Cell Biology, Suzhou, 215121, China.
| | - Lijian Hui
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Bio-Research Innovation Center, Shanghai Institute of Biochemistry and Cell Biology, Suzhou, 215121, China.
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
- School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, 310024, China.
| | - Xiaoqun Wang
- State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Advanced Innovation Center for Human Brain Protection, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China.
| | - Yi Arial Zeng
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- Bio-Research Innovation Center, Shanghai Institute of Biochemistry and Cell Biology, Suzhou, 215121, China.
- School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, 310024, China.
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Salinas-Jazmín N, Rosas-Cruz A, Velasco-Velázquez M. Reporter gene systems for the identification and characterization of cancer stem cells. World J Stem Cells 2021; 13:861-876. [PMID: 34367481 PMCID: PMC8316869 DOI: 10.4252/wjsc.v13.i7.861] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/19/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Cancer stem cells (CSCs) are tumor cells that share functional characteristics with normal and embryonic stem cells. CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo- and radiotherapy, with important roles in tumor progression and the response to therapy. Thus, a current goal of cancer research is to eliminate CSCs, necessitating an adequate phenotypic and functional characterization of CSCs. Strategies have been developed to identify, enrich, and track CSCs, many of which distinguish CSCs by evaluating the expression of surface markers, the initiation of specific signaling pathways, and the activation of master transcription factors that control stemness in normal cells. We review and discuss the use of reporter gene systems for identifying CSCs. Reporters that are under the control of aldehyde dehydrogenase 1A1, CD133, Notch, Nanog homeobox, Sex-determining region Y-box 2, and POU class 5 homeobox can be used to identify CSCs in many tumor types, track cells in real time, and screen for drugs. Thus, reporter gene systems, in combination with in vitro and in vivo functional assays, can assess changes in the CSCs pool. We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics, demonstrating their value in CSCs research.
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Affiliation(s)
- Nohemí Salinas-Jazmín
- Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Arely Rosas-Cruz
- Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Marco Velasco-Velázquez
- Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
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Wangsa D, Braun R, Schiefer M, Gertz EM, Bronder D, Quintanilla I, Padilla-Nash HM, Torres I, Hunn C, Warner L, Buishand FO, Hu Y, Hirsch D, Gaiser T, Camps J, Schwartz R, Schäffer AA, Heselmeyer-Haddad K, Ried T. The evolution of single cell-derived colorectal cancer cell lines is dominated by the continued selection of tumor-specific genomic imbalances, despite random chromosomal instability. Carcinogenesis 2019; 39:993-1005. [PMID: 29800151 DOI: 10.1093/carcin/bgy068] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Revised: 03/13/2018] [Accepted: 05/21/2018] [Indexed: 12/22/2022] Open
Abstract
Intratumor heterogeneity is a major challenge in cancer treatment. To decipher patterns of chromosomal heterogeneity, we analyzed six colorectal cancer cell lines by multiplex interphase FISH (miFISH). The mismatch-repair-deficient cell lines DLD-1 and HCT116 had the most stable copy numbers, whereas aneuploid cell lines (HT-29, SW480, SW620 and H508) displayed a higher degree of instability. We subsequently assessed the clonal evolution of single cells in two colorectal carcinoma cell lines, SW480 and HT-29, which both have aneuploid karyotypes but different degrees of chromosomal instability. The clonal compositions of the single cell-derived daughter lines, as assessed by miFISH, differed for HT-29 and SW480. Daughters of HT-29 were stable, clonal, with little heterogeneity. Daughters of SW480 were more heterogeneous, with the single cell-derived daughter lines separating into two distinct populations with different ploidy (hyper-diploid and near-triploid), morphology, gene expression and tumorigenicity. To better understand the evolutionary trajectory for the two SW480 populations, we constructed phylogenetic trees which showed ongoing instability in the daughter lines. When analyzing the evolutionary development over time, most single cell-derived daughter lines maintained their major clonal pattern, with the exception of one daughter line that showed a switch involving a loss of APC. Our meticulous analysis of the clonal evolution and composition of these colorectal cancer models shows that all chromosomes are subject to segregation errors, however, specific net genomic imbalances are maintained. Karyotype evolution is driven by the necessity to arrive at and maintain a specific plateau of chromosomal copy numbers as the drivers of carcinogenesis.
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Affiliation(s)
- Darawalee Wangsa
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Rüdiger Braun
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Madison Schiefer
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Edward Michael Gertz
- Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD, USA
| | - Daniel Bronder
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Isabel Quintanilla
- Unitat de Biologia Cellular i Genètica Mèdica, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Hesed M Padilla-Nash
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Irianna Torres
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Cynthia Hunn
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Lidia Warner
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Floryne O Buishand
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA.,Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - Yue Hu
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Daniela Hirsch
- Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Timo Gaiser
- Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Jordi Camps
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA.,Unitat de Biologia Cellular i Genètica Mèdica, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Russell Schwartz
- Departments of Biological Sciences and Computational Biology, Carnegie Mellon University, Pittsburgh, PA, USA
| | - Alejandro A Schäffer
- Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD, USA
| | - Kerstin Heselmeyer-Haddad
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
| | - Thomas Ried
- Genetics Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
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Pereira CV, Duarte M, Silva P, Bento da Silva A, Duarte CMM, Cifuentes A, García-Cañas V, Bronze MR, Albuquerque C, Serra AT. Polymethoxylated Flavones Target Cancer Stemness and Improve the Antiproliferative Effect of 5-Fluorouracil in a 3D Cell Model of Colorectal Cancer. Nutrients 2019; 11:E326. [PMID: 30717428 PMCID: PMC6412836 DOI: 10.3390/nu11020326] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 01/26/2019] [Accepted: 01/30/2019] [Indexed: 12/17/2022] Open
Abstract
Polymethoxylated flavones (PMFs) from citrus fruits are reported to present anticancer potential. However, there is a lack of information regarding their effect on cancer stem cell (CSC) populations, which has been recognized as responsible for tumor initiation, relapse, and chemoresistance. In this study, we evaluated the effect of an orange peel extract (OPE) and its main PMFs, namely, nobiletin, sinensetin, tangeretin, and scutellarein tetramethylether in targeting cell proliferation and stemness using a 3D cell model of colorectal cancer composed of HT29 cell spheroids cultured for 7 days in stirred conditions. Soft agar assay, ALDH1 activity, and relative quantitative gene expression analysis of specific biomarkers were carried out to characterize the stemness, self-renewal, and mesenchymal features of HT29 cell spheroids. Then, the impact of OPE and PMFs in reducing cell proliferation and modulating cancer stemness and self-renewal was assessed. Results showed that, when compared with monolayer cultures, HT29 cell spheroids presented higher ALDH1 activity (81.97% ± 5.27% compared to 63.55% ± 17.49% for 2D), upregulation of CD44, PROM1, SOX9, and SNAI1 genes (1.83 ± 0.34, 2.54 ± 0.51, 2.03 ± 0.15, and 6.12 ± 1.59 times) and high self-renewal capability (352 ± 55 colonies compared to 253 ± 42 for 2D). Incubation with OPE (1 mg/mL) significantly inhibited cell proliferation and modulated cancer stemness and self-renewal ability: colony formation, ALDH1 activity, and the expression of cancer stemness biomarkers PROM1 and LGR5 were significantly reduced (0.66 ± 0.15 and 0.51 ± 0.14 times, respectively). Among all PMFs, tangeretin was the most efficient in targeting the CSC population by decreasing colony formation and the expression of PROM1 and LGR5. Scutellarein tetramethylether was shown to modulate markers of mesenchymal/metastatic transition (increasing CDH1 and reducing ZEB1 and SNAI1) and nobiletin was capable of downregulating PROM1 and SNAI1 expression. Importantly, all PMFs and OPE were shown to synergistically interact with 5-fluorouracil, improving the antiproliferative response of this drug.
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Affiliation(s)
- Carolina V Pereira
- iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal.
| | - Marlene Duarte
- Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E (IPOLFG, EPE), 1099-023 Lisboa, Portugal.
| | - Patrícia Silva
- Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E (IPOLFG, EPE), 1099-023 Lisboa, Portugal.
| | - Andreia Bento da Silva
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), 2780-157 Oeiras, Portugal.
- Faculdade de Farmácia da Universidade de Lisboa, Av das Forças Armadas, 1649-019 Lisboa, Portugal.
| | - Catarina M M Duarte
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), 2780-157 Oeiras, Portugal.
| | - Alejandro Cifuentes
- Laboratory of Foodomics, Institute of Food Science Research (CIAL, CSIC), Calle Nicolás Cabrera 9, 28049 Madrid, Spain.
| | - Virginia García-Cañas
- Molecular Nutrition and Metabolism, Institute of Food Science Research (CIAL, CSIC) Calle Nicolás Cabrera 9, 28049 Madrid, Spain.
| | - Maria R Bronze
- iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal.
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), 2780-157 Oeiras, Portugal.
- Faculdade de Farmácia da Universidade de Lisboa, Av das Forças Armadas, 1649-019 Lisboa, Portugal.
| | - Cristina Albuquerque
- Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E (IPOLFG, EPE), 1099-023 Lisboa, Portugal.
| | - Ana Teresa Serra
- iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal.
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), 2780-157 Oeiras, Portugal.
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Azhdarinia A, Voss J, Ghosh SC, Simien JA, Hernandez Vargas S, Cui J, Yu WA, Liu Q, Carmon KS. Evaluation of Anti-LGR5 Antibodies by ImmunoPET for Imaging Colorectal Tumors and Development of Antibody-Drug Conjugates. Mol Pharm 2018; 15:2448-2454. [PMID: 29718672 DOI: 10.1021/acs.molpharmaceut.8b00275] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is highly expressed in colorectal tumors and marks colon cancer stem cells that drive tumor growth and metastasis. Recently, we showed that LGR5 is a promising target for antibody-drug conjugate (ADC) therapy. However, it is important to identify LGR5-positive tumors that would respond to ADC treatment. Prior to drug conjugation, we evaluated two different anti-LGR5 monoclonal antibodies (mAbs), 8F2 and 9G5, using 89Zr-immunoPET to select the optimal mAb for ADC development and tumor imaging. Binding, specificity, and internalization were compared, and mAbs were prescreened as ADC candidates against colon cancer cells using secondary ADCs. Both mAbs demonstrated strong, specific binding in 293T-LGR5 cells but not 293T-vector cells. In DLD-1 colorectal cancer cells, which express high levels of LGR5, the mAbs rapidly internalized into lysosomes and promoted ADC-induced cytotoxicity, with 8F2 exhibiting slightly higher potency. No binding was detected in DLD-1-shLGR5 (LGR5 knockdown) cells. 89Zr-DFO-LGR5 mAbs were generated and shown to retain high affinity and LGR5-dependent uptake in vitro. PET/CT imaging of DLD-1 tumors was performed 5 days postinjection of 89Zr-DFO-LGR5 mAbs, and findings were consistent with biodistribution data, which showed significantly higher tumor uptake (%ID/g) for 89Zr-DFO-8F2 (17.9 ± 2.2) compared to 89Zr-DFO-9G5 (5.5 ± 1.2) and 89Zr-DFO-IgG (3.8 ± 1.0). No significant uptake was observed in DLD-1-shLGR5 tumors. This study identifies 8F2 as the optimal candidate for ADC development and provides initial evidence that 89Zr-DFO-LGR5 mAbs may be utilized to stratify tumors which would respond best to LGR5-targeted ADC therapy.
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Affiliation(s)
| | | | | | | | | | - Jie Cui
- Wntrix, Inc. , Houston , Texas 77021 , United States
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Saygin C, Samour M, Chumakova A, Jarrar A, Lathia JD, Reizes O. Reporter Systems to Study Cancer Stem Cells. Methods Mol Biol 2018; 1516:319-333. [PMID: 27221339 DOI: 10.1007/7651_2016_360] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cancer stem cells have been identified in primary tumors, patient derived xenografts, and established cancer cell lines. The development of reporters has enabled investigators to rapidly enrich for these cells and more importantly track these cells in real time. Here we describe the current state of the reporter field and their use and limitations in multiple cancers.
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Affiliation(s)
- Caner Saygin
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NC 10, Cleveland, OH, 44195, USA
| | - Mohamed Samour
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NC 10, Cleveland, OH, 44195, USA.,Medicine Institute, Cleveland Clinic, Cleveland, OH, 44195, USA
| | - Anastasia Chumakova
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NC 10, Cleveland, OH, 44195, USA
| | - Awad Jarrar
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NC 10, Cleveland, OH, 44195, USA
| | - Justin D Lathia
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NC 10, Cleveland, OH, 44195, USA.,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, 44195, USA.,Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, 44195, USA.,Case Comprehensive Cancer Center, Cleveland, OH, 44106, USA
| | - Ofer Reizes
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NC 10, Cleveland, OH, 44195, USA. .,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, 44195, USA. .,Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, 44195, USA. .,Case Comprehensive Cancer Center, Cleveland, OH, 44106, USA.
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Hirsch D, Ried T. Targeting colorectal cancer (stem-like) cells using LGR5 directed antibody drug conjugates. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:508. [PMID: 28149870 DOI: 10.21037/atm.2016.11.78] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Daniela Hirsch
- Institute of Pathology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany
| | - Thomas Ried
- Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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8
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Chen X, Hao J, Fu T, Liu J, Yu M, He S, Qian R, Zhang F. Temporal and Spatial Expression of LGR5 After Acute Spinal Cord Injury in Adult Rats. Neurochem Res 2016; 41:2645-2654. [DOI: 10.1007/s11064-016-1977-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 06/05/2016] [Accepted: 06/08/2016] [Indexed: 01/21/2023]
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