ArticlePloS one2014
Establishment of highly tumorigenic human colorectal cancer cell line (CR4) with properties of putative cancer stem cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Establishment of Coala: a novel 3D and 2D cancer cell line derived from colorectal cancer liver metastasis.Human cell · 2025Article
- Identification of Growth Factors, Cytokines and Mediators Regulated byInternational journal of molecular sciences · 2022Article
- Preclinical models as patients' avatars for precision medicine in colorectal cancer: past and future challenges.Journal of experimental & clinical cancer research : CR · 2021Review
- Sensitive High-Throughput Assays for Tumour Burden Reveal the Response of aInternational journal of molecular sciences · 2021Article
- Microenvironmentally-driven Plasticity of CD44 isoform expression determines Engraftment and Stem-like Phenotype in CRC cell lines.Theranostics · 2020Article
- Surface expression marker profile in colon cancer cell lines and sphere-derived cells suggests complexity in CD26Biology open · 2019Article
- Three-dimensional cell culture: A powerful tool in tumor research and drug discovery.Oncology letters · 2017Article
- Inflammation and Colorectal Cancer.Current colorectal cancer reports · 2017Article
- Establishment and Characterization of Primary Cultures from Iranian Oral Squamous Cell Carcinoma Patients by Enzymatic Method and Explant Culture.Journal of dentistry (Tehran, Iran) · 2017Article
- Heterogeneity in cancer cells: variation in drug response in different primary and secondary colorectal cancer cell lines in vitro.In vitro cellular & developmental biology. Animal · 2017Article
- Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer.Oncogene · 2017Article
- Hypoxic 3D in vitro culture models reveal distinct resistance processes to TKIs in renal cancer cells.Cell & bioscience · 2017Article
- Microencapsulation of low-passage poorly-differentiated human mucoepidermoid carcinoma cells by alginate microcapsules: in vitro profiling of angiogenesis-related molecules.Cancer cell international · 2017Article
- A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties.Lab on a chip · 2016Article
- CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype.Oncotarget · 2016Article
- Role of CD133Oncology letters · 2016Article
- Characterization of novel low passage primary and metastatic colorectal cancer cell lines.Oncotarget · 2016Article
- Establishment and characterization of a human intrahepatic cholangiocarcinoma cell line derived from an Italian patient.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Cancer stem cells in human digestive tract malignancies.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) has the third highest mortality rates among the US population. According to the most recent concept of carcinogenesis, human tumors are organized hierarchically, and the top of it is occupied by malignant stem cells (cancer stem cells, CSCs, or cancer-initiating cells, CICs), which possess unlimited self-renewal and tumor-initiating capacities and high resistance to conventional therapies. To reflect the complexity and diversity of human tumors and to provide clinically and physiologically relevant cancer models, large banks of characterized patient-derived low-passage cell lines, and especially CIC-enriched cell lines, are urgently needed. PRINCIPAL
findingsHere we report the establishment of a novel CIC-enriched, highly tumorigenic and clonogenic colon cancer cell line, CR4, derived from liver metastasis. This stable cell line was established by combining 3D culturing and 2D culturing in stem cell media, subcloning of cells with particular morphology, co-culture with carcinoma associated fibroblasts (CAFs) and serial transplantation to NOD/SCID mice. Using RNA-Seq complete transcriptome profiling of the tumorigenic fraction of the CR4 cells in comparison to the bulk tumor cells, we have identified about 360 differentially expressed transcripts, many of which represent stemness, pluripotency and resistance to treatment. Majority of the established CR4 cells express common markers of stemness, including CD133, CD44, CD166, EpCAM, CD24 and Lgr5. Using immunocytochemical, FACS and western blot analyses, we have shown that a significant ratio of the CR4 cells express key markers of pluripotency markers, including Sox-2, Oct3/4 and c-Myc. Constitutive overactivation of ABC transporters and NF-kB and absence of tumor suppressors p53 and p21 may partially explain exceptional drug resistance of the CR4 cells.
conclusionsThe highly tumorigenic and clonogenic CIC-enriched CR4 cell line may provide an important new tool to support the discovery of novel diagnostic and/or prognostic biomarkers as well as the development of more effective therapeutic strategies.
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