title: Lumican, a small leucine-rich proteoglycan substituted with keratan sulfate chains is expressed and secreted by human melanoma cells and not normal melanocytes.
abstract: Melanoma is a frequent and therapy-resistant human disease. Malignant melanocytes modulate their microenvironment in order to penetrate the dermal/epidermal junction and eventually invade the dermis. The small leucine-rich proteoglycans (SLRPs) constitute important constituents of the dermis extracellular matrix (ECM), participating in both the structural and the functional organization of the skin. The role of a keratan sulphate SLRP lumican, has recently been investigated in the growth and metastasis of several cancers. In this study, the expression of lumican was studied in two human melanoma cell lines (WM9, M5) as well as in normal neonatal human melanocytes (HEMN) using real time PCR, western blotting with antibodies against the protein core and keratan sulfate, and treatments with specific enzymes. Both human metastatic melanoma cell lines were found to express lumican mRNA and effectively secrete lumican in a proteoglycan form, characterized to be substituted mostly with keratan sulfate chains. Lumican mRNA was not detected in normal melanocytes. This is the first time that the synthesis and secretion of lumican in human melanoma cell lines is reported. The role of this proteoglycan in the development and progression of malignant melanoma has to be further investigated.
authors.affiliation: Department of Dermatology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Sifaki
authors.forename: M
authors.initials: M
authors.lastname: Assouti
authors.forename: D
authors.initials: D
authors.lastname: Nikitovic
authors.forename: K
authors.initials: K
authors.lastname: Krasagakis
authors.forename: N K
authors.initials: NK
authors.lastname: Karamanos
authors.forename: G N
authors.initials: GN
authors.lastname: Tzanakakis
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007632:Keratan Sulfate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000071234:Lumican; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C000604306:LUM protein, human; D000071234:Lumican; D012333:RNA, Messenger; D007632:Keratan Sulfate