Role of CD44 in Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Annual rept. 1 Sep 2001-31 Aug 2002
CINCINNATI UNIV OH
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Malignant peripheral nerve sheath tumors MPNSTs are aggressive malignancies that arise within peripheral nerves. These tumors occur with increased incidence in patients with neurofibromatosis type 1 NF1 where they exhibit increased Ras activity due to toss of the NF1 gene product, neurofibromin, and abnormal expression of the epidermal growth factor receptor EGFR. We previously found that MPNSTs express increased levels of the CD44 family of transmembrane glycoproteins that have been implicated in tumor cell invasion and metastasis. Here we find that CD44 overexpression, driven by Src kinase activity and not increased Ras-GTP contributes to MPNST cell invasion. We further find that EGFR contributes at least part of the elevated Src activity in these cells. CD44 may function in concert with the c-Met receptor tyrosine kinase by promoting an autocrine loop involving the c-Met ligand, hepatocyte growth factor.
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