title: Anti-angiogenesis effect of 3'-sulfoquinovosyl-1'-monoacylglycerol via upregulation of thrombospondin 1.
abstract: We previously reported that 3'-sulfoquinovosyl-1'-monoacylglycerol (SQMG) effectively suppresses the growth of solid tumors, likely via its anti-angiogenic activity. To investigate how SQMG affects angiogenesis, we performed DNA microarray analysis and quantitative real-time polymerase chain reaction. Consequently, upregulation of thrombospondin 1 (TSP-1) in SQMG-treated tumors in vitro and in vivo was confirmed. To address the mechanisms of TSP-1 upregulation by SQMG, we established stable TSP-1-knockdown transformants (TSP1-KT) by short hairpin RNA induction and performed reporter assay and in vivo assessment of anti-tumor assay. On the reporter assay, transcriptional upregulation of TSP-1 in TSP1-KT could not be induced by SQMG, thus suggesting that TSP-1 upregulation by SQMG occurred via TSP-1 molecule. In addition, growth of TSP1-KT xenografted tumors in vivo was not inhibited by SQMG, thus suggesting that anti-angiogenesis via TSP-1 upregulation induced by SQMG did not occur, as the SQMG target molecule TSP-1 was knocked down in TSP1-KT transformants. These data provide that SQMG is a promising candidate for the treatment of tumor-induced angiogenesis via TSP-1 upregulation.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Matsuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanabe
authors.forename: Ayumi
authors.initials: A
authors.lastname: Hongo
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Hiroeki
authors.initials: H
authors.lastname: Sahara
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006017:Glycolipids / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D050178:Monoglycerides / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C104118:3'-sulfonoquinovosyl-1'-monoacylglyceride; D020533:Angiogenesis Inhibitors; D006017:Glycolipids; D050178:Monoglycerides; D019700:Thrombospondin 1