Identification of established and novel extracellular matrix components in glioblastoma as targets for angiogenesis and prognosis
View abstract on PubMed
Summary
This summary is machine-generated.Glioblastomas (GBM) show altered extracellular matrix (ECM) gene expression, impacting blood vessel formation. Neurocan (NCAN) and Collagen 27A1 (COL27A1) are identified as potential new prognostic biomarkers for GBM patients.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- Glioblastomas (GBM) are aggressive brain tumors characterized by rapid growth, resistance to treatment, and extensive blood vessel formation (angiogenesis).
- Endothelial cell (EC) migration and proliferation are crucial for angiogenesis, and these processes are regulated by extracellular matrix (ECM) molecules.
- Previous studies suggest that the GBM microenvironment influences EC behavior, but specific ECM molecules involved remain incompletely understood.
Purpose Of The Study
- To investigate differences in ECM gene expression between GBM and normal brain tissue.
- To analyze the impact of the GBM microenvironment on the ECM transcript profile of human brain microvascular endothelial cells (HBMECs).
- To identify novel ECM molecules that may serve as prognostic biomarkers for GBM.
Main Methods
- In silico analysis of ECM gene expression in GBM versus normal brain tissue.
- Culturing HBMECs on GBM-derived ECM to assess effects on EC numbers.
- Correlation analysis between the expression of identified ECM molecules and GBM patient survival data.
Main Results
- GBM tissue showed significantly increased expression of various ECM genes, including collagen chains (COL4A1, COL4A2), laminins (LAMA4, LAMB2, LAMC1), proteoglycans (NCAN, BCAN, VCAN), and matrix metalloproteinases (MMP2).
- GBM-influenced HBMECs exhibited elevated expression of specific ECM components like COL5A3, COL6A1, COL27A1, LAMA1, LAMB1, and fibulins (FBLN1/2).
- Expression levels of several ECM molecules, including NCAN, COL27A1, and MMPs, correlated significantly with GBM patient survival.
Conclusions
- This study identifies a distinct set of ECM molecules, both known and novel, that are dysregulated in GBM and influence angiogenesis.
- Neurocan (NCAN) and Collagen 27A1 (COL27A1) emerge as promising novel prognostic biomarkers for glioblastoma.
- Targeting these ECM molecules could offer new therapeutic strategies for GBM.
Related Concept Videos
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...

