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• Circulating tumor cells: ready for translation?

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WebPage:
      mainEntity:
         headline:An organoid model of colorectal circulating tumor cells with stem cell features, hybrid EMT state and distinctive therapy response profile
         description:Circulating tumor cells (CTCs) are responsible for the metastatic dissemination of colorectal cancer (CRC) to the liver, lungs and lymph nodes. CTCs rarity and heterogeneity strongly limit the elucidation of their biological features, as well as preclinical drug sensitivity studies aimed at metastasis prevention. We generated organoids from CTCs isolated from an orthotopic CRC xenograft model. CTCs-derived organoids (CTCDOs) were characterized through proteome profiling, immunohistochemistry, immunofluorescence, flow cytometry, tumor-forming capacity and drug screening assays. The expression of intra- and extracellular markers found in CTCDOs was validated on CTCs isolated from the peripheral blood of CRC patients. CTCDOs exhibited a hybrid epithelial-mesenchymal transition (EMT) state and an increased expression of stemness-associated markers including the two homeobox transcription factors Goosecoid and Pancreatic Duodenal Homeobox Gene-1 (PDX1), which were also detected in CTCs from CRC patients. Functionally, CTCDOs showed a higher migratory/invasive ability and a different response to pathway-targeted drugs as compared to xenograft-derived organoids (XDOs). Specifically, CTCDOs were more sensitive than XDOs to drugs affecting the Survivin pathway, which decreased the levels of Survivin and X-Linked Inhibitor of Apoptosis Protein (XIAP) inducing CTCDOs death. These results indicate that CTCDOs recapitulate several features of colorectal CTCs and may be used to investigate the features of metastatic CRC cells, to identify new prognostic biomarkers and to devise new potential strategies for metastasis prevention.
         datePublished:2022-03-08T00:00:00Z
         dateModified:2022-03-08T00:00:00Z
         pageStart:1
         pageEnd:15
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         sameAs:https://doi.org/10.1186/s13046-022-02263-y
         keywords:
            Circulating tumor cells
            Colorectal cancer
            Organoids
            Metastasis
            Cancer stem cells
            Cancer Research
            Immunology
            Apoptosis
            Oncology
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               1756-9966
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      headline:An organoid model of colorectal circulating tumor cells with stem cell features, hybrid EMT state and distinctive therapy response profile
      description:Circulating tumor cells (CTCs) are responsible for the metastatic dissemination of colorectal cancer (CRC) to the liver, lungs and lymph nodes. CTCs rarity and heterogeneity strongly limit the elucidation of their biological features, as well as preclinical drug sensitivity studies aimed at metastasis prevention. We generated organoids from CTCs isolated from an orthotopic CRC xenograft model. CTCs-derived organoids (CTCDOs) were characterized through proteome profiling, immunohistochemistry, immunofluorescence, flow cytometry, tumor-forming capacity and drug screening assays. The expression of intra- and extracellular markers found in CTCDOs was validated on CTCs isolated from the peripheral blood of CRC patients. CTCDOs exhibited a hybrid epithelial-mesenchymal transition (EMT) state and an increased expression of stemness-associated markers including the two homeobox transcription factors Goosecoid and Pancreatic Duodenal Homeobox Gene-1 (PDX1), which were also detected in CTCs from CRC patients. Functionally, CTCDOs showed a higher migratory/invasive ability and a different response to pathway-targeted drugs as compared to xenograft-derived organoids (XDOs). Specifically, CTCDOs were more sensitive than XDOs to drugs affecting the Survivin pathway, which decreased the levels of Survivin and X-Linked Inhibitor of Apoptosis Protein (XIAP) inducing CTCDOs death. These results indicate that CTCDOs recapitulate several features of colorectal CTCs and may be used to investigate the features of metastatic CRC cells, to identify new prognostic biomarkers and to devise new potential strategies for metastasis prevention.
      datePublished:2022-03-08T00:00:00Z
      dateModified:2022-03-08T00:00:00Z
      pageStart:1
      pageEnd:15
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s13046-022-02263-y
      keywords:
         Circulating tumor cells
         Colorectal cancer
         Organoids
         Metastasis
         Cancer stem cells
         Cancer Research
         Immunology
         Apoptosis
         Oncology
      image:
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      author:
            name:Maria Laura De Angelis
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            name:Chiara Nicolazzo
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                     name:Department of Molecular Medicine, Liquid Biopsy Unit, Sapienza University, Rome, Italy
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            name:Michele Signore
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            name:Lidia Colace
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                     name:Department of Surgical Sciences, Policlinico Umberto I/Sapienza University of Rome, Rome, Italy
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            name:Alessandra Boe
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            name:Valentina Magri
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                  name:Sapienza University
                  address:
                     name:Department of Radiological, Oncological and Pathological Sciences, Sapienza University, Rome, Italy
                     type:PostalAddress
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            type:Person
            name:Marta Baiocchi
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            type:Organization
      email:[email protected]
      name:Federica Francescangeli
      affiliation:
            name:Istituto Superiore di Sanità
            address:
               name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Chiara Nicolazzo
      affiliation:
            name:Sapienza University
            address:
               name:Department of Molecular Medicine, Liquid Biopsy Unit, Sapienza University, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Michele Signore
      affiliation:
            name:Istituto Superiore di Sanità
            address:
               name:RPPA Unit, Proteomics Area, Core Facilities, Istituto Superiore di Sanità, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Alessandro Giuliani
      affiliation:
            name:Istituto Superiore di Sanità
            address:
               name:Environment and Health Department, Istituto Superiore di Sanità, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Lidia Colace
      affiliation:
            name:Policlinico Umberto I/Sapienza University of Rome
            address:
               name:Department of Surgical Sciences, Policlinico Umberto I/Sapienza University of Rome, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Alessandra Boe
      affiliation:
            name:Core Facilities, Istituto Superiore di Sanità
            address:
               name:Core Facilities, Istituto Superiore di Sanità, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Valentina Magri
      affiliation:
            name:Sapienza University
            address:
               name:Department of Radiological, Oncological and Pathological Sciences, Sapienza University, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Marta Baiocchi
      affiliation:
            name:Istituto Superiore di Sanità
            address:
               name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Antonio Ciardi
      affiliation:
            name:Policlinico Umberto I/Sapienza University
            address:
               name:Department of Surgery “Pietro Valdoni”, Policlinico Umberto I/Sapienza University, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Francesco Scarola
      affiliation:
            name:Policlinico Umberto I/Sapienza University
            address:
               name:Department of Surgery “Pietro Valdoni”, Policlinico Umberto I/Sapienza University, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Massimo Spada
      affiliation:
            name:Istituto Superiore di Sanità
            address:
               name:Center of Animal Research and Welfare, Istituto Superiore di Sanità, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Filippo La Torre
      affiliation:
            name:Policlinico Umberto I/Sapienza University of Rome
            address:
               name:Surgical Sciences and Emergency Department, Policlinico Umberto I/Sapienza University of Rome, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Paola Gazzaniga
      affiliation:
            name:Sapienza University
            address:
               name:Department of Molecular Medicine, Liquid Biopsy Unit, Sapienza University, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Mauro Biffoni
      affiliation:
            name:Istituto Superiore di Sanità
            address:
               name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Ruggero De Maria
      affiliation:
            name:Università Cattolica del Sacro Cuore
            address:
               name:Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
               type:PostalAddress
            type:Organization
            name:Fondazione Policlinico Universitario A. Gemelli IRCCS
            address:
               name:Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Ann Zeuner
      url:http://orcid.org/0000-0002-8295-3715
      affiliation:
            name:Istituto Superiore di Sanità
            address:
               name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
      name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
      name:Department of Molecular Medicine, Liquid Biopsy Unit, Sapienza University, Rome, Italy
      name:RPPA Unit, Proteomics Area, Core Facilities, Istituto Superiore di Sanità, Rome, Italy
      name:Environment and Health Department, Istituto Superiore di Sanità, Rome, Italy
      name:Department of Surgical Sciences, Policlinico Umberto I/Sapienza University of Rome, Rome, Italy
      name:Core Facilities, Istituto Superiore di Sanità, Rome, Italy
      name:Department of Radiological, Oncological and Pathological Sciences, Sapienza University, Rome, Italy
      name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
      name:Department of Surgery “Pietro Valdoni”, Policlinico Umberto I/Sapienza University, Rome, Italy
      name:Department of Surgery “Pietro Valdoni”, Policlinico Umberto I/Sapienza University, Rome, Italy
      name:Center of Animal Research and Welfare, Istituto Superiore di Sanità, Rome, Italy
      name:Surgical Sciences and Emergency Department, Policlinico Umberto I/Sapienza University of Rome, Rome, Italy
      name:Department of Molecular Medicine, Liquid Biopsy Unit, Sapienza University, Rome, Italy
      name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
      name:Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
      name:Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
      name:Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

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