Role of CD44 in Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Abstract
Malignant peripheral nerve sheath tumors (MPNST) are aggressive, difficult to treat tumors that occur in type I neurofibromatosis patients with an increased incidence compared to the general population. These tumors metastasize to a number of sites, including the lungs, and have a poor 5 year survival rate. We previously found that MPNSTs overexpress the CD44 tranmembrane glycoprotein and that reducing Cc44 expression inhibits MPNST cell invasion. We also found that aberrant CD44 expression is linked to overexpression of the epidermal growth factor receptor (EGFR) in these cells through a Ras-independent mechanism. Here, we provide evidence that EGFR upregulates CD44 expression in the ST88l4 cell line through a mechanism that depends on Src kinase. Furthermore, we show that MPNST cell invasion depends on an autocrine loop involving MCF, an MCF activating enzyme (MGFA), and c-Met, all of which are expressed by MPNST cells. We are currently conducting studies that link CD44 to increased c-Met activity and signaling, and determining the mechanism by which CD44 influences the MCF-c-Met autocrine loop. These studies provide new insights into the mechanisms of MPMST invasion as well as potential targets for the treatment of these tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA396901
Entities
People
- Larry S Sherman
Organizations
- University of Cincinnati