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Periostin accelerates human malignant melanoma progression by modifying the melanoma microenvironment
Author(s) -
Kotobuki Yorihisa,
Yang Lingli,
Serada Satoshi,
Tanemura Atsushi,
Yang Fei,
Nomura Shintaro,
Kudo Akira,
Izuhara Kenji,
Murota Hiroyuki,
Fujimoto Minoru,
Katayama Ichiro,
Naka Tetsuji
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12245
Subject(s) - periostin , melanoma , cancer research , tumor microenvironment , acral lentiginous melanoma , medicine , extracellular matrix , pathology , matricellular protein , biology , microbiology and biotechnology , tumor cells
Summary 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‐ β 1 and TGF‐ β 3. 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.