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F.Ohno, T.Nakahara, M.Nakahara, S.Nunomura, K.Izuhara, M.Furue, Essential role of periostin in inflammation-associated melanoma progression in human and mouse, European Society of Dermatology Research Sep 27, 2017., 2017.09, It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, such a paradigm has not been fully investigated in melanoma. Stromal expression of periostin (S-periostin) is one of the clues to link “inflammation” to “melanoma progression”, because 1) S-periostin is induced in various cutaneous inflammation, 2) S-periostin is involved in tolerogenic M2 macrophage induction, and 3) S-periostin is associated with histological grading of human melanoma. In this study, we first evaluated the prognostic value of S-periostin and found that the intensity of S-periostin was indeed a significant, unfavorable prognostic factor for melanoma (N=94) and that it was also significantly associated with the number of infiltrated M2 macrophages. In murine chronic inflammation model, S-periostin was induced by repeated application of 1% trinitrochlorobenzene every other day for 2 weeks. We then inoculated B16 melanoma cells intradermally into the normal or inflamed murine skin. Three weeks after the inoculation, tumor size in the inflamed skin was significantly larger than that in control skin. Although the number of infiltrated CD3+ T cells was comparable between two groups, significantly more number of CD163+ M2 macrophages were recruited in the melanomas in the inflamed skin than those in control skin. Notably, peritumoral S-periostin was significantly enhanced in the inflamed skin than control. Moreover, periostin receptor αVβ5 integrin was expressed in B16 melanoma cells and periostin significantly upregulated the migration of B16 melanoma cells in vitro. These findings stress a critical role of S-periostin in human and murine melanoma progression and probably prognosis. Furthermore, S-periostin may be implicated in inflammation-associated melanoma progression.. |
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Fumitaka Ohno, Takeshi Nakahara, Makiko Nakahara, Masutaka Furue, Chronic inflammation promotes melanoma progression - emerging role of periostin -, Society for Investigative Dermatology Apr 26, 2017., 2017.04, It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, such a paradigm has not been fully investigated in melanoma. In this study, we inoculated B16 melanoma cells intradermally into the normal or inflamed murine back skin. Chronic inflammation was induced by repeated application of 1% trinitrochlorobenzene every other day for 2 weeks which successfully provided Th1/Th2-intermingled milieu. In a few weeks after inoculation, tumor size in the inflamed skin was significantly larger than that in control skin. Although the number of infiltrated CD3+ T cells was comparable between two groups, significantly more number of CD163+ M2 macrophages were accumulated in the tumor nests of inflamed skin than those in control skin. Notably, tumor nests of inflamed skin were surrounded by higher intensity of periostin compared with those in control skin. In parallel, periostin did promote the tumor growth of B16 melanoma cells in vitro. These findings suggest that chronic inflammation plays a critical role in melanoma progression possibly via periostin induction. In clinical settings, the biologic properties of acral melanomas may be affected by chronic inflammatory events such as repeated friction, trauma and fungal infection.. |
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Ohno F, Nakahara T, Furue M, hree prognostic factors in human melanoma; PD-L1 expression is associated with M2 macrophage infiltration but not with stromal periostin, 5th Eastern Asia Dermatology Congress, 2018.06, Melanoma is one of the most aggressive neoplasia that exhibits poor prognosis and resistance against classic chemotherapy. Currently, immune-checkpoint therapy including anti-programmed cell death 1/ligand 1 (PD-1/PD-L1) antibodies proves to be a clinically effective anti-melanoma treatment. Although much attention has been paid on the PD-1/PD-L1 and T cell pathway, little is known about relationship among this pathway, periostin and M2 macrophage infiltration. We immunohistologically examined the expression of PD-L1, stromal periostin and the infiltration of CD163+ M2 macrophages, and statistically analyzed the association among these variables with the patients’ histological features, clinical stage and prognosis. The PD-L1 expression in melanoma cells was significantly associated with poor prognosis. In addition, either stromal periostin expression or the number of infiltrated CD163+ M2 macrophages had a significant association with poor prognosis. Notably, melanomas with PD-L1 expression had significantly larger number of infiltrated CD163+ M2 macrophages, while the expression of PD-L1 was not correlated with the expression of periostin. These findings pointed a potential linkage between PD-L1 and M2 macrophage in melanoma progression. . |
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Ohno F, Nakahara T, Furue M, Integration of periostin, M2 macrophages and integrin in human and murine melanoma progression, 5th Eastern Asia Dermatology Congress, June 21-24, 2018., 2018.06. |
