title: Proteolysis of the matricellular protein hevin by matrix metalloproteinase-3 produces a SPARC-like fragment (SLF) associated with neovasculature in a murine glioma model.
abstract: The matricellular SPARC-family member hevin (Sparc-like 1/SPARCL-1/SC1/Mast9) contributes to neural development and alters tumor progression in a range of mammalian models. Based on sequence similarity, we hypothesized that proteolytic digestion of hevin would result in SPARC-like fragments (SLF) that affect the activity and/or location of these proteins. Incubation of hevin with matrix metalloproteinase-3 (MMP-3), a protease known to cleave SPARC, produced a limited number of peptides. Sequencing revealed the major proteolytic products to be SPARC-like in primary structure. In gliomas implanted into murine brain, a SLF was associated with SPARC in the neovasculature but not with hevin, the latter prominent in the astrocytes encompassed by infiltrating tumor. In this model of invasive glioma that involves MMP-3 activity, host-derived SLF was not observed in the extracellular matrix adjacent to tumor cells. In contrast, it occurred with its homolog SPARC in the angiogenic response to the tumor. We conclude that MMP-3-derived SLF is a marker of neovessels in glioma, where it could influence the activity of SPARC.
authors.affiliation: Benaroya Research Institute, 1201 Ninth Avenue, Seattle, Washington 98101, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Weaver
authors.forename: Gail
authors.initials: G
authors.lastname: Workman
authors.forename: Chad R
authors.initials: CR
authors.lastname: Schultz
authors.forename: Nancy
authors.initials: N
authors.lastname: Lemke
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Rempel
authors.forename: E Helene
authors.initials: EH
authors.lastname: Sage
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism*; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005910:Glioma / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D015676:Osteonectin / Q000378:metabolism*; D059748:Proteolysis; D014183:Transplantation, Heterologous
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D015676:Osteonectin; C503127:Sparcl1 protein, mouse; D019278:Matrix Metalloproteinase 3