title: Periostin Is a Key Niche Component for Wound Metastasis of Melanoma.
abstract: Tissue injury promotes metastasis of several human cancers, although factors associated with wound healing that attract circulating tumor cells have remained unknown. Here, we examined the primary and metastatic lesions that appeared 1 month after trauma in a patient with acral lentiginous melanoma. The levels of mRNA for periostin (POSTN), type 1 collagen, and fibronectin were significantly increased in the metastatic lesion relative to the primary lesion. The increase of these extracellular matrix proteins at the wound site was reproduced in a mouse model of wound healing, with the upregulation of Postn mRNA persisting the longest. POSTN was expressed in the region surrounding melanoma cell nests in metastatic lesions of both wounded mice and the patient. POSTN attenuated the cell adhesion and promoted the migration of melanoma cells without affecting their proliferation in vitro. In the mouse model, the wound site as well as subcutaneously injected osteoblasts that secrete large amounts of POSTN invited the metastasis of remotely-transplanted melanoma cells on the sites. Osteoblasts with suppression of POSTN by shRNA showed a greatly reduced ability to promote such metastasis. Our results suggest that POSTN is a key factor in promoting melanoma cell metastasis to wound sites by providing a premetastatic niche.
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sugihara
authors.affiliation: Department of Laboratory Medicine, Saga Medical School, Saga, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Funakoshi
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D012867:Skin / Q000293:injuries* / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C082838:Postn protein, mouse