Role of CD44 in Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

摘要

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 CD44 expression partially 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 ST8814 cell line through a inechanism that depends on Src kinase and that Src kinase activity promotes MPNST invasion (Su et al., 2003a) . Furthermore, we show that MPNST cell invasion depends on an autocrine loop involving HGF, an HuF activating enzyme (HGFA), and c-Met, all of which are expressed by MPNST cells (Su et al., 2003b). Interestingly, c-Met - invasion, which may involve Src kinase, and c-Met autocrine activation occur independent of CD44, suggesting that c-Met and Src, but not CD44, are possible targets for anti-metastatic therapies to treat MPNSTs.