Proteoglycans located in basement membranes, the nanos-tructures underling epithelial and endothelial lay-ers, are unique in several respects. They are usually large, elon-gated 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 func-tional 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.

Keywords: agrin, angiogenesis, cancer, collagen XVIII, endorepellin, endostatin, heparan sulfate proteoglycans, perlecan