CNSC-14. ROLE OF A COLLAGEN RECEPTOR, LAIR-1, IN GLIOMA CELLS: A POTENTIAL THERAPEUTIC TARGET. (14th November 2022)

• Record Type: Journal Article
• Authors: Varela, Maria Luisa; Comba, Andrea; Syed, Mohammad Faisal; Murthy, Bhuvna R; Barissi, Marcus N; Castro, Maria; Lowenstein, Pedro
• Is Part Of: Neuro-oncology. Volume 24(2022)Supplement 7
• Page Start: vii24
• Page End: vii25
• Publication Date: 2022-11-14
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac209.095
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Most primary brain tumors are gliomas, among which Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. GBM has a median survival of 15-18 months, and despite extensive research remains incurable. Previous work in our lab has shown the importance of Collagen I, expressed by glioma cells, in glioma growth. Employing genetically engineered mouse models (GEMM) of glioma, NPA (NRas, shP53, shATRX), we identified that Collagen 1α1 (Col1A1) plays a key role in tumor malignancy. Molecular ablation of Col1A1 extends median survival, with a reduction in migration and proliferation. However, the mechanisms underlining these changes in survival, and the receptors mediating these effects remain unknown. Several collagen receptors are present in glioma cells. LAIR-1 is a collagen receptor that was originally described as an inhibitory receptor in hematopoietic cells. Since then, it has been demonstrated that LAIR-1 plays critical roles in the immune imbalance of autoimmune diseases and cancers. There have been several studies postulating the expression of LAIR-1 in tumor cells, including non-hematopoietic tumors. These studies suggest that LAIR-1 may constitute a novel receptor that tumor cells exploit to promote tumor growth and achieve immune evasion, yet its role in glioma remains unclear. Here we describe that glioma cells express LAIR-1, and that its molecular ablation in vitro showed reduced cell proliferation. In addition, GEMM lacking LAIR-1 (NRas, shP53, shATRX, shLAIR-1) exhibit improved median survival. Our preliminary data suggest that LAIR-1 expressed in glioma cells has a role in glioma aggressiveness. Currently we are further characterizing the role of LAIR-1 in high grade gliomas, as well as its potential as a therapeutic target. We hypothesize that blocking the interaction between LAIR-1 and collagen in the tumor microenvironment may improve median survival by reducing tumor proliferation.