For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
6
views
22
references
 Top references
cited by
7
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      811
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Reprogramming of Cancer Cells into Induced Pluripotent Stem Cells Questioned

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background and Objectives

          Several recent studies have claimed that cancer cells can be reprogrammed into induced pluripotent stem cells (iPSCs). However, in most cases, cancer cells seem to be resistant to cellular reprogramming. Furthermore, the underlying mechanisms of limited reprogramming in cancer cells are largely unknown. Here, we identified the candidate barrier genes and their target genes at the early stage of reprogramming for investigating cancer reprogramming.

          Methods

          We tried induction of pluripotency in normal human fibroblasts (BJ) and both human benign (MCF10A) and malignant (MCF7) breast cancer cell lines using a classical retroviral reprogramming method. We conducted RNA-sequencing analysis to compare the transcriptome of the three cell lines at early stage of reprogramming.

          Results

          We could generate iPSCs from BJ, whereas we were unable to obtain iPSCs from cancer cell lines. To address the underlying mechanism of limited reprogramming in cancer cells, we identified 29 the candidate barrier genes based on RNA-sequencing data. In addition, we found 40 their target genes using Cytoscape software.

          Conclusions

          Our data suggest that these genes might one of the roadblock for cancer cell reprogramming. Furthermore, we provide new insights into application of iPSCs technology in cancer cell field for therapeutic purposes.

          Related collections

          Most cited references22

          • Record: found
          • Abstract: not found
          • Article: not found

          The history of cancer epigenetics.

          Andrew Feinberg, Benjamin Tycko (2004)
          Article 0 comments Cited 549 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Defined factors induce reprogramming of gastrointestinal cancer cells.

            Ken-ichi NAGAI, Hideshi Ishii, Hiroaki Nagano … (2010)
            Although cancer is a disease with genetic and epigenetic origins, the possible effects of reprogramming by defined factors remain to be fully understood. We studied the effects of the induction or inhibition of cancer-related genes and immature status-related genes whose alterations have been reported in gastrointestinal cancer cells. Retroviral-mediated introduction of induced pluripotent stem (iPS) cell genes was necessary for inducing the expression of immature status-related proteins, including Nanog, Ssea4, Tra-1-60, and Tra-1-80 in esophageal, stomach, colorectal, liver, pancreatic, and cholangiocellular cancer cells. Induced cells, but not parental cells, possessed the potential to express morphological patterns of ectoderm, mesoderm, and endoderm, which was supported by epigenetic studies, indicating methylation of DNA strands and the histone H3 protein at lysine 4 in promoter regions of pluripotency-associated genes such as NANOG. In in vitro analysis induced cells showed slow proliferation and were sensitized to differentiation-inducing treatment, and in vivo tumorigenesis was reduced in NOD/SCID mice. This study demonstrated that pluripotency was manifested in induced cells, and that the induced pluripotent cancer (iPC) cells were distinct from natural cancer cells with regard to their sensitivity to differentiation-inducing treatment. Retroviral-mediated introduction of iPC cells confers higher sensitivity to chemotherapeutic agents and differentiation-inducing treatment.
            Article 0 comments Cited 114 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells.

              Konrad Hochedlinger, Nimet Maherali, Jochen Utikal … (2009)
              Induced pluripotent stem cells (iPSCs) have been derived at low frequencies from different cell types through ectopic expression of the transcription factors Oct4 and Sox2, combined with either Klf4 and c-Myc or Lin28 and Nanog. In order to generate iPSCs more effectively, it will be crucial to identify somatic cells that are easily accessible and possibly require fewer factors for conversion into iPSCs. Here, we show that both human and mouse melanocytes give rise to iPSCs at higher efficiencies than fibroblasts. Moreover, we demonstrate that a mouse malignant melanoma cell line, which has previously been reprogrammed into embryonic stem cells by nuclear transfer, remains equally amenable to reprogramming into iPSCs by these transcription factors. In contrast to skin fibroblasts, melanocytes and melanoma cells did not require ectopic Sox2 expression for conversion into iPSCs. iPSC lines from melanocytic cells expressed pluripotency markers, formed teratomas and contributed to viable chimeric mice with germ line transmission. Our results identify skin melanocytes as an alternative source for deriving patient-specific iPSCs at increased efficiency and with fewer genetic elements. In addition, our results suggest that cancer cells remain susceptible to transcription factor-mediated reprogramming, which should facilitate the study of epigenetic changes in human cancer.
              Article 0 comments Cited 113 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Stem Cells
                Journal ID (iso-abbrev): Int J Stem Cells
                Journal ID (publisher-id): IJSC
                Title: International Journal of Stem Cells
                Publisher: Korean Society for Stem Cell Research
                ISSN (Print): 2005-3606
                ISSN (Electronic): 2005-5447
                Publication date Collection: 2019
                Publication date (Electronic): 31 August 2019
                Volume: 12
                Issue: 3
                Pages: 430-439
                Affiliations
                [1 ]Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea
                [2 ]Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea
                [3 ]Department of Medicine, College of Medicine, Chung-Ang University, Seoul, Korea
                [4 ]Research Institute of Medical Science, Konkuk University, Seoul, Korea
                Author notes
                Correspondence to: Kinarm Ko, Departement of Stem Cell Biology, Konkuk University School of Medicine, 120 Neungdong-ro, Gwanjin-gu, Seoul 05029, Korea, Tel: +82-2-2030-7888, Fax: +82-2-446-9001, E-mail: knko@ 123456kku.ac.kr
                Article
                Publisher ID: ijsc-12-430
                DOI: 10.15283/ijsc19067
                PMC ID: 6881048
                PubMed ID: 31474029
                SO-VID: b6bd7aa0-cb50-4ffe-9f89-025556464e51
                Copyright © Copyright © 2019 by the Korean Society for Stem Cell Research
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 17 May 2019
                Date revision received : 26 July 2019
                Date accepted : 27 July 2019
                Categories
                Subject: Original Article

                Keywords: induced pluripotent stem cells,ipsc generation,rna-sequencing analysis,pluripotency,cancer cell reprogramming
                Data availability:
                Keywords: induced pluripotent stem cells, ipsc generation, rna-sequencing analysis, pluripotency, cancer cell reprogramming

                Comments

                Comment on this article

                scite_

                Similar content811

                See all similar

                Cited by7

                See all cited by

                Most referenced authors1,116

                See all reference authors