title: SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer.
abstract: SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly posttranslational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand-glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tanaka
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tamura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Aomatsu
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Furuta
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.forename: Kanae
authors.initials: K
authors.lastname: Kudo
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kimura
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
mesh_terms: D045744:Cell Line, Tumor; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006025:Glycosaminoglycans / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C116881:SRPX2 protein, human; D017228:Hepatocyte Growth Factor; D019765:Chondroitin ABC Lyase