The GCTM-5 Epitope Associated with the Mucin-Like Glycoprotein FCGBP Marks Progenitor Cells in Tissues of Endodermal Origin§

Authors

  • Lincon A. Stamp,

    1. Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia
    2. The Australian Stem Cell Centre, Monash University Clayton Campus, Clayton, Victoria, Australia
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  • David R. Braxton,

    1. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, California, USA
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  • Jun Wu,

    1. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, California, USA
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  • Veronika Akopian,

    1. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, California, USA
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  • Kouichi Hasegawa,

    1. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, California, USA
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  • Parakrama T. Chandrasoma,

    1. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California
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  • Susan M. Hawes,

    1. Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia
    2. The Australian Stem Cell Centre, Monash University Clayton Campus, Clayton, Victoria, Australia
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  • Catriona McLean,

    1. Department of Anatomical Pathology, The Alfred Hospital, Prahran, Victoria, Australia
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  • Lydia M. Petrovic,

    1. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California
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  • Kasper Wang,

    1. Saban Research Institute, Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California
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  • Martin F. Pera

    Corresponding author
    1. Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia
    2. The Australian Stem Cell Centre, Monash University Clayton Campus, Clayton, Victoria, Australia
    3. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, California, USA
    • Melbourne Brain Centre, University of Melbourne, 3010 Victoria, Australia
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    • Telephone: +61-3-90356726; Fax +61-3-93495917


  • Author contributions: L.A.S. and D.R.B.: conception and design, collection of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; J.W.: conception and design, collection of data, data analysis and interpretation, and approval of manuscript; V.A.: collection of data; K.H.: conception and design, collection of data, data analysis and interpretation, and final approval of manuscript; P.T.C.: provision of study material and data analysis and interpretation; S.H.: data analysis and interpretation; C.M. and L.M.P.: provision of study material, data analysis and interpretation, and final approval of manuscript; K.W.: financial support, provision of study material, data analysis and interpretation, and final approval of manuscript; M.F.P.: conception and design, financial support, provision of study material, data analysis and interpretation, manuscript writing, and final approval of manuscript. L.A.S., D.R.B., J.W., V.A., and K.H. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS July 3, 2012.

Abstract

Monoclonal antibodies against cell surface markers are powerful tools in the study of tissue regeneration, repair, and neoplasia, but there is a paucity of specific reagents to identify stem and progenitor cells in tissues of endodermal origin. The epitope defined by the GCTM-5 monoclonal antibody is a putative marker of hepatic progenitors. We sought to analyze further the distribution of the GCTM-5 antigen in normal tissues and disease states and to characterize the antigen biochemically. The GCTM-5 epitope was specifically expressed on tissues derived from the definitive endoderm, in particular the fetal gut, liver, and pancreas. Antibody reactivity was detected in subpopulations of normal adult biliary and pancreatic duct cells, and GCTM-5-positive cells isolated from the nonparenchymal fraction of adult liver expressed markers of progenitor cells. The GCTM-5-positive cell populations in liver and pancreas expanded greatly in numbers in disease states such as biliary atresia, cirrhosis, and pancreatitis. Neoplasms arising in these tissues also expressed the GCTM-5 antigen, with pancreatic adenocarcinoma in particular showing strong and consistent reactivity. The GCTM-5 epitope was also strongly displayed on cells undergoing intestinal metaplasia in Barrett's esophagus, a precursor to esophageal carcinoma. Biochemical, mass spectrometry, and immunochemical studies revealed that the GCTM-5 epitope is associated with the mucin-like glycoprotein FCGBP. The GCTM-5 epitope on the mucin-like glycoprotein FCGBP is a cell surface marker for the study of normal differentiation lineages, regeneration, and disease progression in tissues of endodermal origin. Stem Cells2012;30:1999–2009

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