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

Valerio Papa, Riccardo Ricci, Sergio Alfieri, 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, Antonio Sciuto, Tiziana Pia Latiano, Massimo Carella, Dino Amadori, Giulia GalleraniGraziano Pesole, Angelo L. Vescovi, Elena Binda

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

3 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)346-360
Numero di pagine15
RivistaEBioMedicine
Volume44
DOI
Stato di pubblicazionePubblicato - 2019

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

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