EMMPRIN, which is identical to human basigin (CD147), interacts with fibroblasts and stimulates expression of MMPs, which play an important role in tumor invasiveness and metastasis. In the present study, we demonstrated that coculture of basigin‐expressing human MM cells with dermal fibroblasts resulted in the induction of MMP‐1, MMP‐2, MMP‐3 and MT1‐MMP production by fibroblasts and of melanoma cell invasion through a reconstituted basement membrane. Antibody to basigin inhibited both the production of MMPs by fibroblasts and the invasiveness of melanoma cells. Expression of basigin and MMPs in MM and surrounding fibroblasts was examined immunohistochemically in 28 specimens from 18 MM patients without metastasis and 10 with metastasis, to investigate whether basigin plays a role in metastasis of MM in vivo. Basigin was expressed in melanoma cells but not in fibroblasts. MM with metastasis had significantly higher basigin expression compared to MM without metastasis. There were significant differences between MMs with and without metastasis in the expression of MMPs in both melanoma cells and fibroblasts. Expression of MMPs in fibroblasts was positively correlated with expression levels of basigin. These immunohistochemic findings indicate that MMPs might be expressed in fibroblasts as well as melanoma cells concomitantly with basigin, which was expressed in melanoma cells more frequently in MM with metastasis. Basigin is highly expressed in melanoma cells and may play an important role in their invasiveness and metastasis by stimulating surrounding fibroblasts to express MMPs.

The pathogenesis and etiology of systemic sclerosis (SSc) are complex and poorly understood. To date, several studies have demonstrated that the activation of the immune system undoubtedly plays a pivotal role in SSc pathogenesis. Activated immune effector T cells contribute to the release of various pro-inflammatory cytokines and drive the SSc-specific autoantibody responses. This, and a profibrotic environment, are all-important components of abnormal active immune responses that can lead to pathological disorders of SSc. CD11a is essential to inflammatory and immune responses, regulating adhesive and co-stimulatory interactions between CD4+ T cells and other cells. Although CD11a is overexpressed in SSc patients, the mechanisms leading to this overexpression and its consequences remain unclear. DNA methylation, a main epigenetic modification, plays an important role in the regulation of gene expression and is involved in the pathogenesis of autoimmune diseases. This work aims to investigate the effect of DNA demethylation on CD11a expression in SSc CD4+ T cells and to determine its functional significance. CD11a expression was measured using RT-PCR and flow cytometry. Bisulfite sequencing was used to determine the methylation status of the CD11a regulatory region. CD4+ T cells were co-cultured with antigen-presenting cells, B cells, or fibroblasts with and without anti-CD11a, and proliferation of CD4+ T cells, IgG production by B cells, and expression levels of COL1A2 mRNA by fibroblasts were evaluated. Elevated CD11a expression levels were observed in CD4+ T cells from SSc patients; these levels were found to be positively correlated with disease activity. The methylation levels of the CD11a regulatory sequences were lower in SSc patients than in controls and inversely correlated with CD11a mRNA expression. Treatment of CD4+ T cells with 5-azacytidine (5-azaC) decreased CD11a promoter methylation and caused CD11a overexpression. SSc CD4+ T cells and 5-azaC-treated CD4+ T cells showed increased proliferation of CD4+ T cells, increased production of IgG by co-cultured B cells, and induced expression of COL1A2 mRNA by co-cultured fibroblasts. These stimulatory effects were abrogated by anti-CD11a. Demethylation of CD11a regulatory elements and subsequent CD11a overexpression in CD4+ T cells may mediate immunological abnormalities and fibrotic processes in SSc.