Amyloid precursor protein is a biomarker for transformed human pluripotent stem cells

Vivek Venkataramani; Knut Thiele; Carl Ludwig Behnes; Gerald G Wulf; Paul Thelen; Lennart Opitz; Gabriella Salinas-Riester; Oliver Wirths; Thomas A Bayer; Stefan Schweyer

doi:10.1016/j.ajpath.2011.12.015

Amyloid precursor protein is a biomarker for transformed human pluripotent stem cells

Am J Pathol. 2012 Apr;180(4):1636-52. doi: 10.1016/j.ajpath.2011.12.015. Epub 2012 Feb 1.

Authors

Vivek Venkataramani¹, Knut Thiele, Carl Ludwig Behnes, Gerald G Wulf, Paul Thelen, Lennart Opitz, Gabriella Salinas-Riester, Oliver Wirths, Thomas A Bayer, Stefan Schweyer

Affiliation

¹ Division of Molecular Psychiatry, Department of Psychiatry, University Medicine Goettingen, Goettingen, Germany. ramani@med.unigoettingen.de

PMID: 22305861
DOI: 10.1016/j.ajpath.2011.12.015

Abstract

Increasing evidence suggests an important function of the β-amyloid precursor protein (APP) in malignant disease in humans; however, the biological basis for this evidence is not well understood at present. To understand the role of APP in transformed pluripotent stem cells, we studied its expression levels in human testicular germ cell tumors using patient tissues, model cell lines, and an established xenograft mouse model. In the present study, we demonstrate the cooperative expression of APP with prominent pluripotency-related genes such as Sox2, NANOG, and POU5F1 (Oct3/4). The closest homologue family member, APLP2, showed no correlation to these stem cell factors. In addition, treatment with histone deacetylase (HDAC) inhibitors suppressed the levels of APP and stem cell markers. Loss of pluripotency, either spontaneously or as a consequence of treatment with an HDAC inhibitor, was accompanied by decreased APP protein levels both in vitro and in vivo. These observations suggest that APP represents a novel and specific biomarker in human transformed pluripotent stem cells that can be selectively modulated by HDAC inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Amyloid beta-Protein Precursor / genetics
Amyloid beta-Protein Precursor / metabolism*
Amyloid beta-Protein Precursor / pharmacology
Animals
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Cell Differentiation / drug effects
Cell Transformation, Neoplastic / metabolism
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins / metabolism
Histone Deacetylase Inhibitors / pharmacology
Histone Deacetylase Inhibitors / therapeutic use
Humans
Male
Mice
Mice, Nude
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism
Neoplasms, Germ Cell and Embryonal / drug therapy
Neoplasms, Germ Cell and Embryonal / metabolism*
Neoplasms, Germ Cell and Embryonal / pathology
Pluripotent Stem Cells / metabolism*
Protein Processing, Post-Translational / drug effects
Recombinant Proteins / pharmacology
Testicular Neoplasms / drug therapy
Testicular Neoplasms / metabolism*
Testicular Neoplasms / pathology
Transcription, Genetic / drug effects
Tumor Cells, Cultured
Valproic Acid / pharmacology
Valproic Acid / therapeutic use
Xenograft Model Antitumor Assays
Young Adult

Substances

Amyloid beta-Protein Precursor
Biomarkers, Tumor
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Histone Deacetylase Inhibitors
Neoplasm Proteins
Recombinant Proteins
Valproic Acid