Basement Membrane Proteoglycans: Modulators Par Excellence of Cancer Growth and Angiogenesis

Abstract

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.

Epidermal Growth Factor and Perlecan Fragments Produced by Apoptotic Endothelial Cells Co-Ordinately Activate ERK1/2-Dependent Antiapoptotic Pathways in Mesenchymal Stem Cells

“…Urine proteomic analysis identified LG3 as a novel biomarker of CTV in renal transplant recipients [30,31,58]. The present work demonstrates that LG3 could participate in the pathophysiology of CTV through inhibition of apoptotic pathways in hMSC.…”

Basement Membranes: Cell Scaffoldings and Signaling Platforms

“…The heparan sulfate proteoglycans agrin, perlecan, and type XVIII collagen have the potential to tether and accumulate growth factors (Iozzo et al 2009). Such heparin-binding factors include fibroblast growth factors (FGF, especially FGF-2), transforming growth factor-b (TGFb-1,2), bone morphogenic proteins (BMPs-2,4,7), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factors (VEGF), heparin-binding epidermal growth factor (HB-EGF), and neuregulin (Plotnikov et al 1999;Li and Loeb 2001;Rider 2006).…”

Proteomic Analysis of Candidate Prognostic Urinary Marker for Cervical Cancer

“…We found that one tryptic peptide that matched to perlecan by MS/MS, as well as PMF, resided on the C-terminal domain V of perlecan, commonly known as endorepellin (Table 2). Endorepellin blocks endothelial cell migration and capillary morphogenesis, both in vitro and in vivo [26]. Endorepellin interacts specifically with the α2β1 integrin [27], and stimulation with endorepellin induces the interaction and phosphorylation of Src homology-2 protein phosphatase-1 with integrin α2 in endothelial cells [28].…”