This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We and others found that the glycosaminoglycan hyaluronan (HA) accumulates in schwannomas from patients with neurofibromatosis 2 (NF2). Cells respond to HA through one of several transmembrane HA receptors including CD44. CD44 interacts with the NF2 gene product merlin, a tumor suppressor protein1. A high molecular weight form of HA can induce merlin dephosphorylation and activation via CD441. Interestingly, aberrant CD44 splice variants that have enhanced HA affinity are expressed by schwannoma cells that lack merlin in situ, suggesting that HA signaling may be amplified within schwannomas. The goals of this project are: (1) Determine the quality of HA in human schwannomas and how it accumulates; (2) Determine the profile of HA receptors expressed by schwannomas and which receptors are required for HA signaling by schwannoma cells; and (3) Test if HA promotes proliferation in schwannoma cells and Schwann cells that lack merlin in an erbB2-dependent manner. These studies will provide significant clues as to whether inhibiting HA synthesis, degrading HA, or blocking HA signaling might be efficacious strategies to inhibit or at least slow schwannoma growth in patients with NF2.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-49
Application #
7716000
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2008-05-01
Project End
2009-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
49
Fiscal Year
2008
Total Cost
$55,512
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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