Periostin is a key niche component for wound metastasis of melanoma

Keitaro Fukuda, Eiji Sugihara, Shoichiro Ohta, Kenji Izuhara, Takeru Funakoshi, Masayuki Amagai, Hideyuki Saya

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

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.

Original languageEnglish
Article numbere0129704
JournalPloS one
Volume10
Issue number6
DOIs
Publication statusPublished - 17-06-2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General

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