Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/84314
Title:
Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer.
Authors:
Woods, Andrew M; Wang, Who W; Shaw, David M; Ward, Christopher M; Carroll, Miles W; Rees, Buddug R; Stern, Peter L
Abstract:
Human 5T4 oncofoetal antigen defined by the murine 5T4 monoclonal antibody is a highly glycosylated protein expressed by trophoblast and a few specialized adult epithelia. Up-regulation of 5T4 expression in some cancers is associated with poor clinical outcome; overexpression of human 5T4 cDNA in epithelial cells can alter their morphology and motility, supporting a role for such functions in cancer and development. A murine model to study 5T4 biology and tumour immunology would be useful. The production of m5T4-specific antibodies, their use in establishing transfected cells and documenting their biological properties in vitro are described. A rat monoclonal antibody specific for mouse 5T4 molecules by ELISA, flow cytometry, immunohistochemistry and immunoprecipitation was isolated and epitope mapped. Similar to its human counterpart, murine 5T4 antigen is a 72 kDa glycoprotein (immunoprecipitation and Western blot analysis) and exhibits punctate cell surface expression, dependent upon the integrity of the actin cytoskeleton. Likewise, overexpression of autologous murine 5T4 by B16 F10 melanoma cells and A9 L fibroblasts accentuates the 5T4 phenotype, which is characterized by a spindle-like morphology, increased motility, and reduced adhesion and proliferation rate. Immunohistochemical analysis of adult mouse tissues shows a restricted pattern of expression similar to that of human 5T4 antigen. The murine 5T4 antigen-expressing cell lines and antibody reagents are now being used to explore novel immunotherapies in pre-clinical models and the biology of 5T4 in development.
Affiliation:
CRUK Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, U.K.
Citation:
Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer. 2002, 366 (Pt 1):353-65 Biochem. J.
Journal:
The Biochemical Journal
Issue Date:
15-Aug-2002
URI:
http://hdl.handle.net/10541/84314
DOI:
10.1042/BJ20020104
PubMed ID:
12003637
Type:
Article
Language:
en
ISSN:
0264-6021
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWoods, Andrew Men
dc.contributor.authorWang, Who Wen
dc.contributor.authorShaw, David Men
dc.contributor.authorWard, Christopher Men
dc.contributor.authorCarroll, Miles Wen
dc.contributor.authorRees, Buddug Ren
dc.contributor.authorStern, Peter Len
dc.date.accessioned2009-10-16T10:43:59Z-
dc.date.available2009-10-16T10:43:59Z-
dc.date.issued2002-08-15-
dc.identifier.citationCharacterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer. 2002, 366 (Pt 1):353-65 Biochem. J.en
dc.identifier.issn0264-6021-
dc.identifier.pmid12003637-
dc.identifier.doi10.1042/BJ20020104-
dc.identifier.urihttp://hdl.handle.net/10541/84314-
dc.description.abstractHuman 5T4 oncofoetal antigen defined by the murine 5T4 monoclonal antibody is a highly glycosylated protein expressed by trophoblast and a few specialized adult epithelia. Up-regulation of 5T4 expression in some cancers is associated with poor clinical outcome; overexpression of human 5T4 cDNA in epithelial cells can alter their morphology and motility, supporting a role for such functions in cancer and development. A murine model to study 5T4 biology and tumour immunology would be useful. The production of m5T4-specific antibodies, their use in establishing transfected cells and documenting their biological properties in vitro are described. A rat monoclonal antibody specific for mouse 5T4 molecules by ELISA, flow cytometry, immunohistochemistry and immunoprecipitation was isolated and epitope mapped. Similar to its human counterpart, murine 5T4 antigen is a 72 kDa glycoprotein (immunoprecipitation and Western blot analysis) and exhibits punctate cell surface expression, dependent upon the integrity of the actin cytoskeleton. Likewise, overexpression of autologous murine 5T4 by B16 F10 melanoma cells and A9 L fibroblasts accentuates the 5T4 phenotype, which is characterized by a spindle-like morphology, increased motility, and reduced adhesion and proliferation rate. Immunohistochemical analysis of adult mouse tissues shows a restricted pattern of expression similar to that of human 5T4 antigen. The murine 5T4 antigen-expressing cell lines and antibody reagents are now being used to explore novel immunotherapies in pre-clinical models and the biology of 5T4 in development.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAnimals-
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntigens, Neoplasm-
dc.subject.meshBlotting, Western-
dc.subject.meshCell Division-
dc.subject.meshCell Line-
dc.subject.meshCell Membrane-
dc.subject.meshCell Movement-
dc.subject.meshCell Separation-
dc.subject.meshCytoskeleton-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshElectrophoresis, Polyacrylamide Gel-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshEpitope Mapping-
dc.subject.meshEpitopes-
dc.subject.meshFlow Cytometry-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshImmunotherapy-
dc.subject.meshLeucine-
dc.subject.meshMembrane Glycoproteins-
dc.subject.meshMice-
dc.subject.meshMicroscopy, Fluorescence-
dc.subject.meshNeoplasms-
dc.subject.meshPrecipitin Tests-
dc.subject.meshRats-
dc.subject.meshRecombinant Fusion Proteins-
dc.titleCharacterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer.en
dc.typeArticleen
dc.contributor.departmentCRUK Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, U.K.en
dc.identifier.journalThe Biochemical Journalen

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