Plasminogen activating inhibitor-1 (PAI-1) is classically known as an angiogenesis promoting factor that is associated with poor clinical outcomes in various cancers, including skin cancer such as cutaneous melanomas. Cutaneous angiosarcoma (CAS) is a vascular tumor histologically characterized by detachment of endothelial cell-derived tumor cells. Since CAS expresses multiple angiogenic growth factors and has increased expressions of angiogenic receptor tyrosine kinase transcripts including VEGFR1/2/3, angiogenesis-promoting factors are potential drug targets in CAS. In this study, at first, the expression of PAI-1 was examined in 31 cases of CAS, and next, the immunomodulatory effects of PAI-1 on a human CAS cell line, ISO-HAS-B, were evaluated. We found that, of the angiogenesis-promoting factors, PAI-1 was expressed in 93.5% (29 of 31) of CAS, and even intensely expressed in 64.5% of CAS (20 of 31) cases. In vitro analysis revealed that PAI-1 increased the mRNA expressions of IL-23p19, VEGF-C, CXCL5, and CCL20 on ISO-HAS-B. IL-23p19 and CCL20 production from ISO-HAS-B was validated by ELISA. Moreover, immunohistochemical staining for CAS showed that IL-23p19 was expressed in 61.3% of cases, and VEGF-C was expressed in 41% of cases. In addition, CCL20 producing cells and IL-17 producing cells were detected in the lesional skin of CAS. Notably, the serum levels of VEGF-C and CXCL5 tended to correlate with disease activity in each case of CAS treated with eribulin mesylate. The results of the present study suggest that PAI-1 promotes angiogenesis that results in tumor progression in CAS, and PAI-1 inhibitors might be a potential drug for CAS.

ESDR457 - Plasminogen activating inhibitor-1 could be a key factor for the induction of angiogenesis in cutaneous angiosarcomas

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.