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Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy

  • Go J Yoshida1,
  • Yasushi Fuchimoto2Email author,
  • Tomoo Osumi3,
  • Hiroyuki Shimada3,
  • Seiichi Hosaka4,
  • Hideo Morioka4,
  • Makio Mukai5,
  • Yohei Masugi6,
  • Michiie Sakamoto6 and
  • Tatsuo Kuroda7
BMC Cancer201212:444

Received: 15 July 2012

Accepted: 27 September 2012

Published: 2 October 2012

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Archived Comments

  1. Ectopic or Drastic Increase of CSCs after Chemotherapy

    6 November 2014

    Go Yoshida, Tokyo Medical and Dental University

    As shown in Figure-4 of this case report, conventional chemotherapy is considered to be partially responsible for the increase of cancer stem cells (CSCs) in number in vivo. The recent Nature article entitled as “Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function” investigated into the drastic proliferation of mutant KRAS-driven pancreatic ductal adenocarcinoma CSCs utilizing the Tet-ON/OFF and ON system. Notably, they have also revealed the metabolic features of CSCs to depend more on mitochondria as compared with non-CSCs or before oncogene ablation.

    Ref: Nature 514, 628–632 (30 October 2014)

    Competing interests

    No competing interests exist.

  2. Potential cancer stem-like cells of this atypical hepatic cancer in the Li-Fraumeni syndrome 

    13 August 2015

    Go Yoshida, Tokyo Medical and Dental University

    It has recently been identified the presence of liver stem cells located near to the central vein with the method of lineage tracing focusing on Wnt-responsive gene Axin2 in mice.1,2 Central vein endothelial cells, which secrete Wnt9b ligand, correspond to niche to maintain the homeostasis and the zonation of liver lobules,2 whereas Lgr5-positive oval hepatic stem-like cells rapidly respond to the injury and exhibit robust self-renewal proliferation.3 It is also notable that the former diploid stem cells retain unlimited replicative potential,2,4 which can partially explain the reasons why hepatic tumor cells often lack tumor suppressor genes such as APC or Axin,1 and also they arise exclusively from cells located near to the central vein in the case of c-Met overexpression.4,5 Given that CD44 is one of the canonical Wnt signal target molecules,6 cancer stem cells of the atypical hepatic tumor developed in a patient with germline mutation of p53 may emerge from peri-central lesion in the liver lobule.



    1: Laurent-Puig P, Zucman-Rossi J. Genetics of hepatocellular tumors. Oncogene 2006;25:3778-86.

    2: Wang B, Zhao L, Fish M, Logan CY, Nusse R. Self-renewing diploid Axin2 cells fuel homeostatic renewal of the liver. Nature 2015.

    3: Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 2013;494:247-50

    4: Schwarze PE, Pettersen EO, Shoaib MC, Seglen PO. Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis. Carcinogenesis 1984;5:1267-75.

    5: Tward AD, Jones KD, Yant S, et al. Distinct pathways of genomic progression to benign and malignant tumors of the liver. Proceedings of the National Academy of Sciences of the United States of America 2007;104:14771-6

    6: Yoshida GJ, Saya H. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation. Biochemical and biophysical research communications 2014;443:622-7.

    Competing interests

    There are no competing interests to be addressed.

Authors’ Affiliations

Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Division of Surgery, Department of Surgical Subspecialities, National Center for Child Health and Development, Tokyo, Japan
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan
Department of Orthopedic Surgery, Keio University School of Medicine, Japan
Division of Diagnostic Pathology, Keio University Hospital, Tokyo, Japan
Department of Pathology, Keio University School of Medicine, Tokyo, Japan
Department of Pediatric Surgey, Keio University School of Medicine, Tokyo, Japan