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

نویسندگان

  • Kaori Shimazaki
  • Eric J Lepin
  • Bo Wei
  • Agnes K Nagy
  • Catherine P Coulam
  • Sergey Mareninov
  • Maoyong Fu
  • Anna M Wu
  • James D Marks
  • Jonathan Braun
  • Lynn K Gordon
  • Madhuri Wadehra
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer.

PURPOSE The tetraspan protein epithelial membrane protein-2 (EMP2) has been shown to regulate the surface display and signaling from select integrin pairs, and it was recently identified as a prognostic biomarker in human endometrial cancer. In this study, we assessed the role of EMP2 in human ovarian cancer. EXPERIMENTAL DESIGN We examined the expression of EMP2 within a population of women ...

متن کامل

Evaluation of cytotoxic effects of condition medium from amniotic epithelial cells on cancer cell lines HeLa and MDA-MB-231

Introduction: Amniotic membrane, the innermost layer of extra-embryonic tissue, contains mesenchymal and epithelial stem cells. The amniotic mesenchymal cells have the capability of inhibition of growth of cancer cells. In this research, the effects of amniotic epithelial cells on the viability of cancer cells and the role of apoptosis in this procedure were evaluated. Methods: Amniotic mem...

متن کامل

PK11195 enhances chemosensitivity to cisplatin and paclitaxel in human endometrial and ovarian cancer cells.

The potential anticancer agent 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein ligand, facilitates the induction of cell death by a variety of cytotoxic and chemotherapeutic agents in various human tumor cell lines. The purpose of this study was to elucidate the effect of PK11195 on three endometrial cancer cell lines, two ovarian cancer cell lines ...

متن کامل

بررسی اثر آنتی‌بادی‌های منوکلونال ضد hCG، بر روی رده سلول‌های سرطانی انسان

Background: Human cancer cell lines express human choriogonadotropin (hCG), its subunits and derivatives, regardless of their origin and type. It appears that hCG is a common phenotype in human cancer cell lines. In this research, the effects of hCG targeting monoclonal antibodies (7D9, T18H7 and T8B12) on human cancer cell lines were evaluated. Methods:  Monoclonal antibody secreting hy...

متن کامل

Epigenetic regulation of CD133 and tumorigenicity of CD133 positive and negative endometrial cancer cells

BACKGROUND Recent data provide significant evidence to support the hypothesis that there are sub-populations of cells within solid tumors that have an increased tumor initiating potential relative to the total tumor population. CD133, a cell surface marker expressed on primitive cells of neural, hematopoietic, endothelial and epithelial lineages has been identified as a marker for tumor initiat...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 14 22  شماره 

صفحات  -

تاریخ انتشار 2008