SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer

• Published in: PloS one 2012-01, Vol.7 (1), p.e27922
• Main Authors: Tanaka, Kaoru, Arao, Tokuzo, Tamura, Daisuke, Aomatsu, Keiichi, Furuta, Kazuyuki, Matsumoto, Kazuko, Kaneda, Hiroyasu, Kudo, Kanae, Fujita, Yoshihiko, Kimura, Hideharu, Yanagihara, Kazuyoshi, Yamada, Yasuhide, Okamoto, Isamu, Nakagawa, Kazuhiko, Nishio, Kazuto
• Format: Article
• Language: English
• Subjects: Analysis; Angiogenesis; Antibodies; Architecture; Biology; Cancer; Cell Line, Tumor; Chondroitin; Chondroitin ABC lyase; Chondroitin ABC Lyase - metabolism; Chondroitin sulfate; Chondroitin Sulfate Proteoglycans - metabolism; Chromatography; Colorectal cancer; Colorectal Neoplasms - genetics; Fluorides; Gastric cancer; Gastrointestinal cancer; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - metabolism; Gene Expression Regulation, Neoplastic; Genomes; Glycosaminoglycans; Glycosaminoglycans - metabolism; Growth factors; Hepatocyte growth factor; Hepatocyte Growth Factor - metabolism; Humans; Hypoxia; Immunoglobulins; Leukemia; Mediation; Medicine; Mutation; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Oncology; Physics; Post-translational modifications; Protein Binding; Protein Processing, Post-Translational; Proteins; Proteoglycans; Seizures; Stomach cancer; Sulfate; Sulfates
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0027922

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.