The Role of EMMPRIN in Tumor Angiogenesis and Metastasis

Abstract

A critical step in trumorigenesis is proteolytic modification of the peri-cellular matrix surrounding tumor cells by matrix metalloproteinases (MMPs). Stromal cells associated with tumors are responsible for the production of most tumor MMPs. Studies from our laboratory and those of our collaborators have shown that EMMPRIN (extracellular matrix metalloproteinase inducer), a tumor cell surface glycoprotein, stimulates the production of several MMPs by fibroblasts and endothelial cells. Antisense cDNA and ribozyme constructs were utilized in an attempt to inhibit EMMPRIN expression in TA3/ST cells, a murine breast carcinoma cell line. These constructs were not efficient in blocking EMMPRIN expression and consequently, were inactive in vivo. However, transfection and injection experiments done in collaboration with Dr. Stanley Zucker have shown that MDA-MB-436 human breast cancer cells transfected with GFP-EMMPRIN produce much larger tumors in nude mice than vector-transfected cells. These same EMMPRIN- transfected cells become more invasive than their control counterparts both in vivo and in a Boyden chamber invasion assay and they exhibit enhanced levels of MMP-2. To confirm this invasive phenotype and extend this phenomenon to non-cancerous cells, we have employed a Matrigel invasion chamber assay. MDA-MB-436, MCF-7 (mammary carcinoma) and MDCK (canine kidney epithelial) cells were either transfected with EMMPRIN or infected with a full-length EMMPRIN recombinant adenovims and then placed in the Matrigel chambers for 24 for 48 hours. The number of cells that invaded were then counted and compared with controls. In each case, elevated EMMPRIN expression corresponded to increased invasiveness over controls. We will further explore this avenue with MCF10A and HMT-3522 Sl cells (mammary epithelial cells) as well as determine an elevation in MMPs corresponding with this phenotype.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2001
Accession Number
ADA391908

Entities

People

  • Bryan Toole
  • Erica Marieb

Organizations

  • Tufts University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Abstracts
  • Angiogenesis
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cells
  • Classification
  • Electronic Mail
  • Endothelial Cells
  • Epithelial Cells
  • Information Operations
  • Neoplasms
  • Security
  • Stromal Cells

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Oncology (Cancer Research).