Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors.
Identifieur interne : 002079 ( PubMed/Corpus ); précédent : 002078; suivant : 002080Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors.
Auteurs : Cassy M. Spiller ; Ad J M. Gillis ; Guillaume Burnet ; Hans Stoop ; Peter Koopman ; Josephine Bowles ; Leendert H J. LooijengaSource :
- Molecular oncology [ 1878-0261 ] ; 2016.
English descriptors
- KwdEn :
- Animals, Carcinoma, Embryonal (blood), Carcinoma, Embryonal (diagnosis), Carcinoma, Embryonal (genetics), Epidermal Growth Factor (biosynthesis), Epidermal Growth Factor (genetics), Epigenesis, Genetic, GPI-Linked Proteins (biosynthesis), GPI-Linked Proteins (genetics), Gene Expression Regulation, Neoplastic, Humans, Intercellular Signaling Peptides and Proteins (biosynthesis), Intercellular Signaling Peptides and Proteins (genetics), Male, Membrane Glycoproteins (biosynthesis), Membrane Glycoproteins (genetics), Mice, Mice, Transgenic, Neoplasm Proteins (biosynthesis), Neoplasm Proteins (genetics), Testicular Neoplasms (blood), Testicular Neoplasms (diagnosis), Testicular Neoplasms (genetics).
- MESH :
- chemical , biosynthesis : Epidermal Growth Factor, GPI-Linked Proteins, Intercellular Signaling Peptides and Proteins, Membrane Glycoproteins, Neoplasm Proteins.
- blood : Carcinoma, Embryonal, Testicular Neoplasms.
- diagnosis : Carcinoma, Embryonal, Testicular Neoplasms.
- genetics : Carcinoma, Embryonal, Epidermal Growth Factor, GPI-Linked Proteins, Intercellular Signaling Peptides and Proteins, Membrane Glycoproteins, Neoplasm Proteins, Testicular Neoplasms.
- Animals, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Transgenic.
Abstract
Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co-receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non-seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non-seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.
DOI: 10.1016/j.molonc.2015.11.003
PubMed: 26654129
Links to Exploration step
pubmed:26654129Le document en format XML
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<author><name sortKey="Looijenga, Leendert H J" sort="Looijenga, Leendert H J" uniqKey="Looijenga L" first="Leendert H J" last="Looijenga">Leendert H J. Looijenga</name>
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<series><title level="j">Molecular oncology</title>
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<term>Carcinoma, Embryonal (blood)</term>
<term>Carcinoma, Embryonal (diagnosis)</term>
<term>Carcinoma, Embryonal (genetics)</term>
<term>Epidermal Growth Factor (biosynthesis)</term>
<term>Epidermal Growth Factor (genetics)</term>
<term>Epigenesis, Genetic</term>
<term>GPI-Linked Proteins (biosynthesis)</term>
<term>GPI-Linked Proteins (genetics)</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>Humans</term>
<term>Intercellular Signaling Peptides and Proteins (biosynthesis)</term>
<term>Intercellular Signaling Peptides and Proteins (genetics)</term>
<term>Male</term>
<term>Membrane Glycoproteins (biosynthesis)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Neoplasm Proteins (biosynthesis)</term>
<term>Neoplasm Proteins (genetics)</term>
<term>Testicular Neoplasms (blood)</term>
<term>Testicular Neoplasms (diagnosis)</term>
<term>Testicular Neoplasms (genetics)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Epidermal Growth Factor</term>
<term>GPI-Linked Proteins</term>
<term>Intercellular Signaling Peptides and Proteins</term>
<term>Membrane Glycoproteins</term>
<term>Neoplasm Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Carcinoma, Embryonal</term>
<term>Testicular Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Carcinoma, Embryonal</term>
<term>Testicular Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Carcinoma, Embryonal</term>
<term>Epidermal Growth Factor</term>
<term>GPI-Linked Proteins</term>
<term>Intercellular Signaling Peptides and Proteins</term>
<term>Membrane Glycoproteins</term>
<term>Neoplasm Proteins</term>
<term>Testicular Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Epigenesis, Genetic</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
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<front><div type="abstract" xml:lang="en">Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co-receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non-seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non-seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.</div>
</front>
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<Title>Molecular oncology</Title>
<ISOAbbreviation>Mol Oncol</ISOAbbreviation>
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<ArticleTitle>Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors.</ArticleTitle>
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<Abstract><AbstractText>Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co-receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non-seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non-seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.</AbstractText>
<CopyrightInformation>Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.</CopyrightInformation>
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<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Spiller</LastName>
<ForeName>Cassy M</ForeName>
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<Initials>J</Initials>
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</AffiliationInfo>
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<ForeName>Leendert H J</ForeName>
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<AffiliationInfo><Affiliation>Department of Pathology, Erasmus MC - University Medical Center, Rotterdam, 3015, The Netherlands. Electronic address: l.looijenga@erasmusmc.nl.</Affiliation>
</AffiliationInfo>
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<CommentsCorrections RefType="Cites"><RefSource>Stem Cells. 2005 Feb;23(2):166-85</RefSource>
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<PMID Version="1">15856041</PMID>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
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<MeshHeading><DescriptorName UI="D018236" MajorTopicYN="Y">Carcinoma, Embryonal</DescriptorName>
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<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
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<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
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<MeshHeading><DescriptorName UI="D015972" MajorTopicYN="Y">Gene Expression Regulation, Neoplastic</DescriptorName>
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<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
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<MeshHeading><DescriptorName UI="D036341" MajorTopicYN="Y">Intercellular Signaling Peptides and Proteins</DescriptorName>
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<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
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<MeshHeading><DescriptorName UI="D008562" MajorTopicYN="Y">Membrane Glycoproteins</DescriptorName>
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<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
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<MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName>
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<MeshHeading><DescriptorName UI="D009363" MajorTopicYN="Y">Neoplasm Proteins</DescriptorName>
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<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
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<MeshHeading><DescriptorName UI="D013736" MajorTopicYN="Y">Testicular Neoplasms</DescriptorName>
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<Keyword MajorTopicYN="N">Diagnostic</Keyword>
<Keyword MajorTopicYN="N">Methylation</Keyword>
<Keyword MajorTopicYN="N">Testicular germ cell cancer</Keyword>
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