Basement membrane-specific heparan sulfate proteoglycan core protein (HSPG2) (HSPG2)

Perlecan (HSPG2) is a massive, modular heparan sulfate proteoglycan that serves as a fundamental component of basement membranes and the extracellular matrix across diverse tissues (UniProt P98160). It consists of five distinct structural domains that interact with a variety of ligands, including growth factors such as FGF and VEGF, basement membrane proteins like laminin and collagen IV, and cell surface receptors including integrins and alpha-dystroglycan (PubMed 19633742). Biologically, perlecan is essential for vasculogenesis, chondrogenesis, and the maintenance of the endothelial barrier, acting as a reservoir and co-receptor for growth factors to regulate cell proliferation and differentiation (PubMed 12733024). In oncology, perlecan is frequently overexpressed in aggressive tumors like triple-negative breast cancer, where it facilitates angiogenesis and metastasis, making it a target for inhibitory antibodies and antibody-drug conjugates (PubMed 31462657, PubMed 38198277). Conversely, its C-terminal fragment, endorepellin (Domain V), possesses potent anti-angiogenic and neuroprotective properties, leading to its investigation as a therapeutic agent for ischemic stroke and neurodegenerative diseases (PubMed 23706013). Mutations in the HSPG2 gene lead to severe skeletal and neuromuscular conditions such as Schwartz-Jampel syndrome and Silverman-Handmaker dyssegmental dysplasia (PubMed 11561274).

Other names

PerlecanPLCPRCANSJASJSSJS1Heparan sulfate proteoglycan 2

Monoclonal antibodies target Domain 1 of perlecan to inhibit growth factor presentation and induce antibody-dependent cell-mediated cytotoxicity (ADCC) or serve as antibody-drug conjugate (ADC) carriers. Recombinant Domain V (Endorepellin) interacts with alpha2beta1 and alpha5beta1 integrins and VEGFR2 to modulate angiogenesis, provide neuroprotection, and stabilize the blood-brain barrier.