title: Periostin accelerates human malignant melanoma progression by modifying the melanoma microenvironment.
abstract: Given no reliable therapy for advanced malignant melanoma, it is important to elucidate the molecular mechanisms underlying the disease progression. Using a quantitative proteomics approach, the 'isobaric tags for relative and absolute quantitation (iTRAQ)' method, we identified that the extracellular matrix protein, periostin (POSTN), was highly expressed in invasive melanoma compared with normal skin. An immunohistochemical analysis showed that POSTN was expressed in all invasive melanoma (n = 20) and metastatic lymph node (n = 5) tissue samples, notably restricted in their stroma. In terms of the intercellular regulation of POSTN, we found that there was upregulation of POSTN when melanoma cells and normal human dermal fibroblasts (NHDFs) were cocultured, with restricted expression of TGF-β1 and TGF-β3. In a functional analyses, recombinant and NHDF-derived POSTN significantly accelerated melanoma cell proliferation via the integrin/mitogen-activated protein kinase (MAPK) signaling pathway in vitro. The size of implanted melanoma tumors was significantly suppressed in POSTN/Rag2 double knockout mice compared with Rag2 knock-out mice. These results indicate that NHDF-derived POSTN accelerates melanoma progression and might be a promising therapeutic target for malignant melanoma.
authors.affiliation: Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan; Laboratory for Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan.
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Kotobuki
authors.forename: Lingli
authors.initials: L
authors.lastname: Yang
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanemura
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nomura
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D059016:Tumor Microenvironment
chemical_list: D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; C512835:POSTN protein, human
keywords: malignant melanoma; periostin; tumor microenvironment