Csig-33. Beta 1 Integrin Inhibition in High-grade Meningioma
Year: 2017
Type: conference-abstract
Abstract: High-grade meningiomas (HGM, World Health Organization classification grade II and III) have high relapse rates and poor clinical outcomes despite surgery and radiation treatments. Developing novel therapeutic strategies requires identification of molecules that drive progression of HGM. Beta 1 integrin (CD29) has been implicated in a variety of malignant characteristics in cancer that include tumor cell adhesion, proliferation and drug resistance. However, the role of beta 1 integrin in meningioma is not understood. We are studying the potential utility of targeting beta 1 integrin as a new approach to treat HGM. OS2966, a humanized antagonizing monoclonal antibody against beta 1 integrin, decreased phosphorylation of MAPK ERK1/2 in the NF2 wild-type IOMM-Lee malignant meningioma cell line and NF2-deficient primary culture tumor-sphere cells, MN3, that we established from a malignant meningioma patient (Nigim et al, Neuro-Oncology 2016). OS2966 inhibited Tyr397 phosphorylation of FAK, a shared downstream effector of NF2 and beta 1-integrin pathways, in MN3, but not in IOMM-Lee cells. In vitro cell viability assay demonstrated that OS2966 suppressed MN3 viability by 50% at 20 ug/ml, but had no effect on IOMM-Lee cell viability at up to 500 ug/ml. These data suggest that beta 1 integrin may promote tumorigenesis of a subset of HGM driven by NF2 loss and/or FAK activation, revealing a potential therapeutic target. We are currently studying anti-tumor effects of systemic administration of OS2966 in the orthotopic HGM model of MN3 in SCID mice, and plan to report results at the meeting.
Source: Neuro-Oncology
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767445508