Understanding of these attributes at the molecular level may offer opportunities for therapeutic intervention.K E Y W O R D S perlecan heparan sulfate proteoglycan tumor angiogenesis vascular endothelial growth factor fibroblast growth factor B asement membranes that separate epithelial, endothelial, muscle, and fat cells from the surrounding connective tissue.The major components of BM are type IV collagen, laminin, entacinnidogen, and heparan sulfate proteoglycans. The ro les of mammalian per lecan and heparinbinding angiogenic vascular endothelial growth factor in tumor growth and angiogenesis are also addressed.The distribution of perlecan in the dermalepidermal junction. The intronexon junctions in the various modules of human perlecan are remarkably conserved, suggesting that the perlecan gene might have evolved from an ancestral gene by gene duplication or exon shuffling.The core protein of mouse perlecan is encoded by a kb mRNA with a deduced MW of kD. kb mRNA with a deduced MW of kD. Nematode perlecan, encoded by the unc gene, spans more than kb of genomic DNA on chromosome II and consists of exons.The longest potential open reading frame of the unc gene encodes a aminoacid protein with a MW of kD. Proteins containing SEA modules are generally composed of multimodule domains, which share homology with other known proteins.When it is deleted from a perlecan domain IIII construct, the heparan sulfate content is increased, suggesting that the SEA module may enhance HS attachment receptor like repeat.Domains IIV of perlecan are therefore well conserved but mammalian domain I has no invertebrate equivalent.Larger mRNA transcripts have been identified in mouse EHS tumor tissue and melanoma M cells, indicating that alternative splicing occurs in domain IV.Complex patterns of alternative splicing have been observed in nematode perlecanUNC.The long isoforms contain all five domains, the medium isoforms contain the first four domains, and the short isoforms contain the first three domains. In addition, alternative splicing of exons, and results in more diversity within domains III and IV. The alternative splicing of exons, and is regulated by the mec. The mec gene encodes a nuclear protein that promotes the splicing of exon directly to or exon directly to, resulting in the accumulation of a specific subset of alternatively spliced perlecan unc transcripts. A presumptive null mutation in smu suppresses nonsense mutations in exon but not in exon, indicating that SMU regulates the splicing of exon, which is skipped in the absence of functional SMU. No information about the GAG substitution on perlecan UNC has been reported thus far.The HS Fosfomycin calcium chains interact with a number of ECM molecules including laminin, type IV collagen, and fibronectin. Doma in IV canbind entact in nidogen and, fibulin, and Betamethasone fibronectin, and domain V binds fibulin and lamininentactinnidogen complex. The binding sites for perlecan on entactinnidogen have been mapped to the G and G domains. It is suggested that BM is composed of two networks, one formed by laminin, and the other formed by type IV collagen.These two networks are connected by entactinnidogen. Perlecan makes such supramolecular architecture more stable by interacting with laminin, type IV collagen, and entactinnidogen.