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http://purl.uniprot.org/citations/18927294http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18927294http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Tumor targeting therapy is one of the most promising strategies for anticancer treatment. Derlin-1 has been reported to participate in misfolded protein dislocation and integrates into the endoplasmic reticulum (ER) membrane to survey for such protein aggregates. We elucidate herein that Derlin-1 can leak to the plasmalemma from the ER in tumor cells and may have clinical application as a novel cancer target in the hope of developing a new tumor targeting therapy.

Experimental design

The cell surface expression of Derlin-1 was shown by immunofluorescence analysis of nonpermeabilized cells and Western blotting of fractional proteins of tumor cells. Derlin-1 expression in cancerous tissues was also shown by immunohistochemistry. Biodistribution analysis and gamma-scintigraphic imaging were done using (125)I-labeled Derlin-1 targeting antibody in isogenic mice models. Finally, tumor-bearing mice were treated by the anti-Derlin-1 polyclonal antibody and monoclonal antibodies.

Results

Derlin-1 was expressed on various tumor cell surfaces and adopted a homodimer conformation. Robust cytoplasmic and membrane expression of Derlin-1 was detected in various types of human cancers tissues but was not correlated with any clinicopathologic features of pancreatic cancer. Derlin-1 directed antibodies specifically targeted to colon tumors and significantly suppress tumor growth in isogenic mice.

Conclusions

These preclinical data show that Derlin-1 protein is a functional molecular target expressed on the tumor cell surface and is a candidate therapeutic target that may be translated into clinical applications."xsd:string
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http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Hu H."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Liu T."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Pan J."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Sun Y."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Sun L."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Zhou Z."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Ran Y."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Yang Z."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Yu L."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/author"Hu D."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/pages"6538-6545"xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/title"Derlin-1 is overexpressed on the tumor cell surface and enables antibody-mediated tumor targeting therapy."xsd:string
http://purl.uniprot.org/citations/18927294http://purl.uniprot.org/core/volume"14"xsd:string
http://purl.uniprot.org/citations/18927294http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18927294
http://purl.uniprot.org/citations/18927294http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18927294
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http://purl.uniprot.org/uniprot/#_E5RGY0-mappedCitation-18927294http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18927294
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