Derlin-1 Is overexpressed on the tumor cell surface and enables antibody-mediated tumor targeting therapy

Yuliang Ran, Hai Hu, Dong Hu, Zhuan Zhou, Yuemin Sun, Long Yu, Lixin Sun, Jian Pan, Jun Liu, Tong Liu, Zhihua Yang*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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. Biodistribu-tion analysis and γ-scintigraphic imaging were done using 125I-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.

Original languageEnglish (US)
Pages (from-to)6538-6545
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number20
DOIs
StatePublished - Oct 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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