Role of Hyaluronan in Schwannoma Growth; Final rept. 1 Jun 2007-31 May 2008

摘要

Schwannomas are benign peripheral nerve tumors that occur in individuals with neurofibromatosis 2 and schwannomatosis. Although schwannomas occur due to mutations in the neurofibromatosis 2 gene, which encodes the merlin tumor suppressor protein, recent studies indicate that schwannoma growth may depend in part on signaling by the erbB2 receptor tyrosine kinase. We previously found that erbB2 signaling depended on interactions between erbB2 and the CD44 transmembrane glycoprotein. CD44 is the receptor for hyaluronan, a glycosaminoglycan found in most extracellular matrices. Here, we found that schwannomas contain 2-3 fold higher levels of a high molecular weight form of hyaluronan compared to normal human peripheral nerve tissue. This elevated hyaluornan is due in part to increased transcription of the hyaluronan synthase gene, HAS2. Elevated hyaluronan correlated with increased phosphorylated (e.g. active) erbB2. These data support the hypothesis that hyaluronan may contribute to schwannoma growth.