Endothelial Cell Behavior Is Determined by Receptor Clustering Induced by Thrombospondin-1

The thrombospondins (TSPs) are a family of multimeric extracellular matrix proteins that dynamically regulate cellular behavior and response to stimuli. In so doing, the TSPs directly and indirectly affect biological processes such as embryonic development, wound healing, immune response, angiogenesis, and cancer progression. Many of the direct effects of Thrombospondin 1 (TSP-1) result from the engagement of a wide range of cell surface receptors including syndecans, low density lipoprotein receptor-related protein 1 (LRP1), CD36, integrins, and CD47. Different or even opposing outcomes of TSP-1 actions in certain pathologic contexts may occur, depending on the structural/functional domain involved. To expedite response to external stimuli, these receptors, along with vascular endothelial growth factor receptor 2 (VEGFR2) and Src family kinases, are present in specific membrane microdomains, such as lipid rafts or tetraspanin-enriched microdomains. The molecular organization of these membrane microdomains and their constituents is modulated by TSP-1. In this review, we will describe how the presence of TSP-1 at the plasma membrane affects endothelial cell signal transduction and angiogenesis.

Automated summary

Thrombospondins (TSPs) are a family of extracellular matrix proteins that regulate cellular behavior and influence biological processes such as angiogenesis and cancer progression. Thrombospondin 1 (TSP-1) interacts with cell surface receptors to have varying effects on cellular behavior depending on the context. Specific membrane microdomains containing receptors like VEGFR2 and Src family kinases are modulated by TSP-1, impacting endothelial cell signal transduction and angiogenesis.