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.

Visioli, A., Giani, F., Trivieri, N., Pracella, R., Miccinilli, E., Cariglia, M., et al. (2019). Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies. EBIOMEDICINE, 44, 346-360 [10.1016/j.ebiom.2019.04.049].

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

Giani F.;Trivieri N.;Vescovi A. L.
Penultimo
;
2019

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.
Articolo in rivista - Articolo scientifico
Anti-CRC SCs strategies; CRC biology and biomarkers; CRC circulating stem cells; CRC metastatic stem cells; CRC stem cells; Human colorectal carcinoma (CRC); Stemness; Animals; Biomarkers; Cell Transformation, Neoplastic; Colorectal Neoplasms; DNA Copy Number Variations; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fluorescent Antibody Technique; Heterografts; Humans; Immunohistochemistry; Loss of Heterozygosity; Mice; Neoplasm Grading; Neoplasm Staging; Neoplastic Cells, Circulating; Neoplastic Stem Cells; Cell Self Renewal
English
2019
44
346
360
open
Visioli, A., Giani, F., Trivieri, N., Pracella, R., Miccinilli, E., Cariglia, M., et al. (2019). Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies. EBIOMEDICINE, 44, 346-360 [10.1016/j.ebiom.2019.04.049].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/272358
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