Basement membrane proteoglycans: modulators Par Excellence of cancer growth and angiogenesis.
Proteoglycans located in basement membranes, the nanostructures underling epithelial and endothelial layers, are unique in several respects. They are usually large, elongated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more "active configuration" to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical for the evolution of the tumor microenvironment. This review will focus on the functional roles of the major heparan sulfate proteoglycans from basement membrane zones: perlecan, agrin and collagen XVIII, and on their roles in modulating cancer growth and angiogenesis.
Iozzo
Renato V
RV
Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. iozzo@mail.jci.tju.edu
Zoeller
Jason J
JJ
Nyström
Alexander
A
D018171:Agrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000494:Allosteric Regulation; D000818:Animals; D001485:Basement Membrane; D048708:Cell Growth Processes; D043170:Collagen Type XVIII / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D005346:Fibroblast Growth Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018171:Agrin; D043170:Collagen Type XVIII; D019812:Heparan Sulfate Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C071927:perlecan; D005346:Fibroblast Growth Factors