Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition
Cancer stem cells (CSC) are crucial mediators of cancer relapse. Here, we isolated two primary human colorectal cancer cell lines derived from a rectal neuroendocrine carcinoma (BKZ-2) and a colorectal adenocarcinoma (BKZ-3), both containing subpopulations with potential stem-like properties. Protei...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/9/2582 |
| _version_ | 1797554059902713856 |
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| author | Jan Schulte am Esch Beatrice Ariane Windmöller Johannes Hanewinkel Jonathan Storm Christine Förster Ludwig Wilkens Martin Krüger Barbara Kaltschmidt Christian Kaltschmidt |
| author_facet | Jan Schulte am Esch Beatrice Ariane Windmöller Johannes Hanewinkel Jonathan Storm Christine Förster Ludwig Wilkens Martin Krüger Barbara Kaltschmidt Christian Kaltschmidt |
| author_sort | Jan Schulte am Esch |
| collection | DOAJ |
| description | Cancer stem cells (CSC) are crucial mediators of cancer relapse. Here, we isolated two primary human colorectal cancer cell lines derived from a rectal neuroendocrine carcinoma (BKZ-2) and a colorectal adenocarcinoma (BKZ-3), both containing subpopulations with potential stem-like properties. Protein expression of CSC-markers prominin-1 and CD44 antigen was significantly higher for BKZ-2 and BKZ-3 in comparison to well-established colon carcinoma cell lines. High sphere-formation capacity further confirmed the existence of a subpopulation with potential stem-like phenotype. Epithelial–mesenchymal transition markers as well as immune checkpoint ligands were expressed more pronounced in BKZ-2. Both cell populations demonstrated N-myc proto-oncogene (<i>NMYC</i>) copy number gain. Myc proto-oncogene (MYC)/NMYC activity inhibitor all-trans retinoic acid (ATRA) significantly reduced the number of tumor spheres for both and the volume of BKZ-2 spheres. In contrast, the sphere volume of ATRA-treated BKZ-3 was increased, and only BKZ-2 cell proliferation was reduced in monolayer culture. Treatment with KJ-Pyr-9, a specific inhibitor of MYC/NMYC-myc-associated factor X interaction, decreased survival by the induction of apoptosis of both. In summary, here, we present the novel colorectal cancer cell lines BKZ-2 and BKZ-3 as promising cellular in vitro models for colorectal carcinomas and identify the MYC/NMYC molecular pathway involved in CSC-induced carcinogenesis with relevant therapeutic potential. |
| first_indexed | 2024-03-10T16:25:26Z |
| format | Article |
| id | doaj.art-5bf52b9d8a444e05bad9b2d199f72c47 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:25:26Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5bf52b9d8a444e05bad9b2d199f72c472023-11-20T13:15:03ZengMDPI AGCancers2072-66942020-09-01129258210.3390/cancers12092582Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC InhibitionJan Schulte am Esch0Beatrice Ariane Windmöller1Johannes Hanewinkel2Jonathan Storm3Christine Förster4Ludwig Wilkens5Martin Krüger6Barbara Kaltschmidt7Christian Kaltschmidt8Department of General and Visceral Surgery, Protestant Hospital of Bethel Foundation, 33611 Bielefeld, GermanyForschungsverbund BioMedizin Bielefeld (FBMB), 33611 Bielefeld, GermanyDepartment of Cell Biology, University of Bielefeld, 33611 Bielefeld, GermanyForschungsverbund BioMedizin Bielefeld (FBMB), 33611 Bielefeld, GermanyForschungsverbund BioMedizin Bielefeld (FBMB), 33611 Bielefeld, GermanyForschungsverbund BioMedizin Bielefeld (FBMB), 33611 Bielefeld, GermanyForschungsverbund BioMedizin Bielefeld (FBMB), 33611 Bielefeld, GermanyForschungsverbund BioMedizin Bielefeld (FBMB), 33611 Bielefeld, GermanyForschungsverbund BioMedizin Bielefeld (FBMB), 33611 Bielefeld, GermanyCancer stem cells (CSC) are crucial mediators of cancer relapse. Here, we isolated two primary human colorectal cancer cell lines derived from a rectal neuroendocrine carcinoma (BKZ-2) and a colorectal adenocarcinoma (BKZ-3), both containing subpopulations with potential stem-like properties. Protein expression of CSC-markers prominin-1 and CD44 antigen was significantly higher for BKZ-2 and BKZ-3 in comparison to well-established colon carcinoma cell lines. High sphere-formation capacity further confirmed the existence of a subpopulation with potential stem-like phenotype. Epithelial–mesenchymal transition markers as well as immune checkpoint ligands were expressed more pronounced in BKZ-2. Both cell populations demonstrated N-myc proto-oncogene (<i>NMYC</i>) copy number gain. Myc proto-oncogene (MYC)/NMYC activity inhibitor all-trans retinoic acid (ATRA) significantly reduced the number of tumor spheres for both and the volume of BKZ-2 spheres. In contrast, the sphere volume of ATRA-treated BKZ-3 was increased, and only BKZ-2 cell proliferation was reduced in monolayer culture. Treatment with KJ-Pyr-9, a specific inhibitor of MYC/NMYC-myc-associated factor X interaction, decreased survival by the induction of apoptosis of both. In summary, here, we present the novel colorectal cancer cell lines BKZ-2 and BKZ-3 as promising cellular in vitro models for colorectal carcinomas and identify the MYC/NMYC molecular pathway involved in CSC-induced carcinogenesis with relevant therapeutic potential.https://www.mdpi.com/2072-6694/12/9/2582colorectal cancer stem cellsNMYCMYCATRAEMTKJ-Pyr-9 |
| spellingShingle | Jan Schulte am Esch Beatrice Ariane Windmöller Johannes Hanewinkel Jonathan Storm Christine Förster Ludwig Wilkens Martin Krüger Barbara Kaltschmidt Christian Kaltschmidt Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition Cancers colorectal cancer stem cells NMYC MYC ATRA EMT KJ-Pyr-9 |
| title | Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition |
| title_full | Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition |
| title_fullStr | Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition |
| title_full_unstemmed | Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition |
| title_short | Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition |
| title_sort | isolation and characterization of two novel colorectal cancer cell lines containing a subpopulation with potential stem like properties treatment options by myc nmyc inhibition |
| topic | colorectal cancer stem cells NMYC MYC ATRA EMT KJ-Pyr-9 |
| url | https://www.mdpi.com/2072-6694/12/9/2582 |
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