Periostin links skin inflammation to melanoma progression in humans and mice

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Abstract

It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a murine inflammatory skin model and investigated the relationship between skin inflammation and melanoma progression. In a murine model, B16F10 melanoma cells in inflamed skin grew significantly more rapidly than cells in control skin. The stromal expression of periostin was upregulated in inflamed skin, and significantly more CD163 + M2 macrophages were recruited to the melanomas in inflamed skin. We then immunohistologically examined the expression of stromal periostin and the infiltration of CD163 + M2 macrophages in human acral lentiginous melanomas (n = 94) and analyzed the statistical associations with clinicopathological variables. In human melanomas, high periostin expression and a large number of infiltrated M2 macrophages were significantly correlated with poor prognosis. Furthermore, we confirmed that periostin promotes the proliferation of murine and human melanoma cells in vitro. Our findings indicate that periostin and M2 macrophages play a critical role in melanoma progression and prognosis in both humans and mice, indicating that periostin is a potential target for treating progressive melanoma.

Original languageEnglish
Article number169
JournalInternational journal of molecular sciences
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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macrophages
progressions
mice
Melanoma
Skin
Macrophages
Inflammation
prognosis
cells
infiltration
tumors
Infiltration
Tumors
Carcinogenesis
Extremities

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

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title = "Periostin links skin inflammation to melanoma progression in humans and mice",
abstract = "It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a murine inflammatory skin model and investigated the relationship between skin inflammation and melanoma progression. In a murine model, B16F10 melanoma cells in inflamed skin grew significantly more rapidly than cells in control skin. The stromal expression of periostin was upregulated in inflamed skin, and significantly more CD163 + M2 macrophages were recruited to the melanomas in inflamed skin. We then immunohistologically examined the expression of stromal periostin and the infiltration of CD163 + M2 macrophages in human acral lentiginous melanomas (n = 94) and analyzed the statistical associations with clinicopathological variables. In human melanomas, high periostin expression and a large number of infiltrated M2 macrophages were significantly correlated with poor prognosis. Furthermore, we confirmed that periostin promotes the proliferation of murine and human melanoma cells in vitro. Our findings indicate that periostin and M2 macrophages play a critical role in melanoma progression and prognosis in both humans and mice, indicating that periostin is a potential target for treating progressive melanoma.",
author = "Fumitaka Ono and Takeshi Nakahara and Makiko Nakahara and Takamichi Ito and Satoshi Nunomura and Kenji Izuhara and Masutaka Furue",
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AU - Ono, Fumitaka

AU - Nakahara, Takeshi

AU - Nakahara, Makiko

AU - Ito, Takamichi

AU - Nunomura, Satoshi

AU - Izuhara, Kenji

AU - Furue, Masutaka

PY - 2019/1/1

Y1 - 2019/1/1

N2 - It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a murine inflammatory skin model and investigated the relationship between skin inflammation and melanoma progression. In a murine model, B16F10 melanoma cells in inflamed skin grew significantly more rapidly than cells in control skin. The stromal expression of periostin was upregulated in inflamed skin, and significantly more CD163 + M2 macrophages were recruited to the melanomas in inflamed skin. We then immunohistologically examined the expression of stromal periostin and the infiltration of CD163 + M2 macrophages in human acral lentiginous melanomas (n = 94) and analyzed the statistical associations with clinicopathological variables. In human melanomas, high periostin expression and a large number of infiltrated M2 macrophages were significantly correlated with poor prognosis. Furthermore, we confirmed that periostin promotes the proliferation of murine and human melanoma cells in vitro. Our findings indicate that periostin and M2 macrophages play a critical role in melanoma progression and prognosis in both humans and mice, indicating that periostin is a potential target for treating progressive melanoma.

AB - It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a murine inflammatory skin model and investigated the relationship between skin inflammation and melanoma progression. In a murine model, B16F10 melanoma cells in inflamed skin grew significantly more rapidly than cells in control skin. The stromal expression of periostin was upregulated in inflamed skin, and significantly more CD163 + M2 macrophages were recruited to the melanomas in inflamed skin. We then immunohistologically examined the expression of stromal periostin and the infiltration of CD163 + M2 macrophages in human acral lentiginous melanomas (n = 94) and analyzed the statistical associations with clinicopathological variables. In human melanomas, high periostin expression and a large number of infiltrated M2 macrophages were significantly correlated with poor prognosis. Furthermore, we confirmed that periostin promotes the proliferation of murine and human melanoma cells in vitro. Our findings indicate that periostin and M2 macrophages play a critical role in melanoma progression and prognosis in both humans and mice, indicating that periostin is a potential target for treating progressive melanoma.

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