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.
Highlights
Inflammation is recognized as a hallmark of cancer development and progression [1,2,3]
The intensity of stromal periostin expression was significantly associated with the number of infiltrated M2 macrophages, and the number of infiltrated M2 macrophages was associated with the poor prognosis of melanoma patients
These results suggested that inflammation is potentially involved in driving melanoma progression
Summary
Inflammation is recognized as a hallmark of cancer development and progression [1,2,3]. It was reported that melanoma cells that expressed a higher level of COX-2 co-expressed a higher level of programmed death ligand 1 (PD-L1) These reports supported the critical involvement of inflammation in melanoma progression. The intensity of stromal periostin expression was significantly associated with the number of infiltrated M2 macrophages, and the number of infiltrated M2 macrophages was associated with the poor prognosis of melanoma patients. These findings indicate that periostin plays a critical role in human and murine melanoma progression and the prognosis of patients with melanoma
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