Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies

Alberto Visioli, Fabrizio Giani, Nadia Trivieri, Riccardo Pracella, Elide Miccinilli, Maria Grazia Cariglia, Orazio Palumbo, Andrea Arleo, Fabio Dezi, Massimiliano Copetti, Laura Cajola, Silvia Restelli, Valerio Papa, Antonio Sciuto, Tiziana Pia Latiano, Massimo Carella, Dino Amadori, Giulia Gallerani, Riccardo Ricci, Sergio AlfieriGraziano Pesole, Angelo L. Vescovi, Elena Binda

Research output: Contribution to journalArticle

Abstract

Background: Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings: We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation: Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund: This work was financially supported by grants from “Ministero della Salute Italiano”(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from “Associazione Italiana Cancro” (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

Original languageEnglish
JournalEBioMedicine
DOIs
Publication statusPublished - Jan 1 2019

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Stem cells
Colorectal Neoplasms
Stem Cells
Tumors
Cells
Circulating Neoplastic Cells
Therapeutics
Organized Financing
Biomarkers
Cardiovascular System
Blood Vessels
Neoplasms

Keywords

  • Anti-CRC SCs strategies
  • CRC biology and biomarkers
  • CRC circulating stem cells
  • CRC metastatic stem cells
  • CRC stem cells
  • Human colorectal carcinoma (CRC)
  • Stemness

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies. / Visioli, Alberto; Giani, Fabrizio; Trivieri, Nadia; Pracella, Riccardo; Miccinilli, Elide; Cariglia, Maria Grazia; Palumbo, Orazio; Arleo, Andrea; Dezi, Fabio; Copetti, Massimiliano; Cajola, Laura; Restelli, Silvia; Papa, Valerio; Sciuto, Antonio; Latiano, Tiziana Pia; Carella, Massimo; Amadori, Dino; Gallerani, Giulia; Ricci, Riccardo; Alfieri, Sergio; Pesole, Graziano; Vescovi, Angelo L.; Binda, Elena.

In: EBioMedicine, 01.01.2019.

Research output: Contribution to journalArticle

Visioli, Alberto ; Giani, Fabrizio ; Trivieri, Nadia ; Pracella, Riccardo ; Miccinilli, Elide ; Cariglia, Maria Grazia ; Palumbo, Orazio ; Arleo, Andrea ; Dezi, Fabio ; Copetti, Massimiliano ; Cajola, Laura ; Restelli, Silvia ; Papa, Valerio ; Sciuto, Antonio ; Latiano, Tiziana Pia ; Carella, Massimo ; Amadori, Dino ; Gallerani, Giulia ; Ricci, Riccardo ; Alfieri, Sergio ; Pesole, Graziano ; Vescovi, Angelo L. ; Binda, Elena. / Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies. In: EBioMedicine. 2019.
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abstract = "Background: Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings: We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation: Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund: This work was financially supported by grants from “Ministero della Salute Italiano”(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from “Associazione Italiana Cancro” (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.",
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AU - Visioli, Alberto

AU - Giani, Fabrizio

AU - Trivieri, Nadia

AU - Pracella, Riccardo

AU - Miccinilli, Elide

AU - Cariglia, Maria Grazia

AU - Palumbo, Orazio

AU - Arleo, Andrea

AU - Dezi, Fabio

AU - Copetti, Massimiliano

AU - Cajola, Laura

AU - Restelli, Silvia

AU - Papa, Valerio

AU - Sciuto, Antonio

AU - Latiano, Tiziana Pia

AU - Carella, Massimo

AU - Amadori, Dino

AU - Gallerani, Giulia

AU - Ricci, Riccardo

AU - Alfieri, Sergio

AU - Pesole, Graziano

AU - Vescovi, Angelo L.

AU - Binda, Elena

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings: We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation: Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund: This work was financially supported by grants from “Ministero della Salute Italiano”(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from “Associazione Italiana Cancro” (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

AB - Background: Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings: We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation: Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund: This work was financially supported by grants from “Ministero della Salute Italiano”(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from “Associazione Italiana Cancro” (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

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