title: Sulfatides inhibit adhesion, migration, and invasion of murine melanoma B16F10 cell line in vitro.
abstract: Endogenous sulfatide, such as 3-sulfated galactosylceramide (3-sulfatide) has been reported to be involved in neuronal development and regulation of tumor cell metastasis. Recently, a new 6-sulfated glucosylceramide (6-sulfatide) has been isolated from the ascidian, Ciona intestinalis. To determine the antitumor function of the new sulfatide, we examined the effects of synthetic 6-sulfatide and 3-sulfatide on the metastatic features of a murine melanoma cell line, B16F10. Both sulfatides significantly inhibited the adhesion of melanoma cells onto fibronectin-coated tissue plates and, the motility and invasion of the cells, with 6-sulfatide showing stronger inhibitory activities. In addition, both sulfatides inhibited α(5)-, and β(1)- but not α(v)- or β(3)-integrin expression. Furthermore, these sulfatides inhibited the activation of focal adhesion kinase, Akt, and extracellular signal-regulated kinase signaling pathways, which are thought to be important for cell migration and invasion. Therefore, these sulfatides may serve as promising drug candidates for the treatment of cancer metastasis.
authors.affiliation: Faculty of Pharmacy, Keio University, 1–5–30 Shibakoen, Tokyo 105–8512, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ozawa
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Saori
authors.initials: S
authors.lastname: Kato
authors.forename: Erika
authors.initials: E
authors.lastname: Suzuki
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Matsuoka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaya
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Kiuchi
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005353:Fibronectins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D039482:Integrin alpha5 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005353:Fibronectins; D039482:Integrin alpha5; D019012:Integrin beta1; D013433:Sulfoglycosphingolipids; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases