Display Settings:

Format

Send to:

Choose Destination
Clin Cancer Res. 2008 Nov 15;14(22):7367-77. doi: 10.1158/1078-0432.CCR-08-1016.

Diabodies targeting epithelial membrane protein 2 reduce tumorigenicity of human endometrial cancer cell lines.

Author information

  • 1Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.

Abstract

PURPOSE:

Endometrial cancer is the most common gynecologic malignancy. One promising biomarker is epithelial membrane protein 2 (EMP2), and its expression is an independent prognostic indicator for tumors with poor clinical outcome expression. The present study assesses the suitability of EMP2 as a therapeutic target.

EXPERIMENTAL DESIGN:

Human monovalent anti-EMP2 antibody fragments were isolated from a human phage display library and engineered as bivalent antibody fragments (diabodies) with specificity and avidity to both EMP2 peptides and native cell-surface EMP2 protein. Diabodies were assessed using cell death and apoptosis assays. In addition, the efficacy of EMP2 diabodies on endometrial cancer tumors was determined using mouse xenograft models.

RESULTS:

Treatment of human endometrial adenocarcinoma cell lines with anti-EMP2 diabodies induced significant cell death and caspase-3 cleavage in vitro. These responses correlated with cellular EMP2 expression and were augmented by progesterone, which physiologically induces EMP2 expression. In vivo, treatment of subcutaneous human xenografts of HEC-1A cell lines with anti-EMP2 diabodies suppressed tumor growth and induced cell death in the xenograft.

CONCLUSIONS:

These findings suggest that EMP2 may be a potential pharmacologic target for human endometrial cancer.

PMID:
19010852
[PubMed - indexed for MEDLINE]
PMCID:
PMC3109074
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk