Basement membranes: structure, assembly and role in tumour angiogenesis

Key Points Vascular basement membranes (BMs) are important structural and functional components of all blood vessels/capillaries and have a crucial role in determining the progression of cancer. Constituents of vascular BMs, such as type IV collagen, laminin, SPARC and perlecan, have emerged as key regulators of angiogenesis. Type IV collagen and laminin can exert both positive and negative regulation of angiogenesis, depending on their structural integrity and assembly. Cryptic domains of type IV collagen can be liberated by proteolytic enzymes, such as matrix metalloproteinases, to expose novel integrin binding sites and angiogenesis inhibitory sequences. Arrestin, canstatin, tumstatin and endostatin are novel BM-derived endogenous inhibitors of angiogenesis. Not all vascular BMs are the same, providing a novel tissue-specific regulation of endothelial-cell behaviour and possibly the rate of cancer progression in a given organ. In recent years, the basement membrane (BM) — a specialized form of extracellular matrix (ECM) — has been recognized as an important regulator of cell behaviour, rather than just a structural feature of tissues. The BM mediates tissue compartmentalization and sends signals to epithelial cells about the external microenvironment. The BM is also an important structural and functional component of blood vessels, constituting an extracellular microenvironment sensor for endothelial cells and pericytes. Vascular BM components have recently been found to be involved in the regulation of tumour angiogenesis, making them attractive candidate targets for potential cancer therapies.