Deletion of endothelial α-parvin inhibits tumour angiogenesis, reduces tumour growth and induces tumour cell apoptosis.
Yara OnettiRoland E KälinBettina PitterMengzhuo HouVictor ArribasRainer GlassEloi MontanezPublished in: Angiogenesis (2022)
Alpha-parvin (α-pv), an adaptor protein that mediates integrin-dependent cell-matrix interactions, is essential for endothelial cells migration and proliferation and is a key player in physiological angiogenesis. The role of α-pv in pathological angiogenesis is unknown. Here we demonstrate that endothelial α-pv is required for tumour angiogenesis. Using an inducible knockout approach in which the α-pv gene (Parva) was inactivated specifically in endothelial cells of brain tumour-bearing mice, we show that loss of endothelial α-pv results in reduced vessel density and decreased vascular complexity of the pathological neo-vasculature without affecting the structure of the brain vasculature around tumour. Reduced tumour vascularisation is associated with a significant increase in tumour cell apoptosis and a reduction in tumour volume. Together, our data show for the first time that endothelial α-pv is required for tumour vascularisation and tumour progression in vivo.
Keyphrases
- endothelial cells
- vascular endothelial growth factor
- cell proliferation
- signaling pathway
- type diabetes
- machine learning
- metabolic syndrome
- adipose tissue
- white matter
- mesenchymal stem cells
- transcription factor
- small molecule
- multiple sclerosis
- functional connectivity
- artificial intelligence
- resting state
- cerebral ischemia
- wild type