Hypoxia accelerates the progression of angiosarcoma through the regulation of angiosarcoma cells and tumor microenvironment

Abstract Background Angiosarcomais a rare malignant tumor with a poor prognosis. It is known that hypoxic condition activates tumor progressionin several cancers. Additionally, hypoxic tumor microenvironmentaccelerates immune escape. However, the presence and significance of hypoxia in angiosarcomahas not been adequately investigated. Objective To study the role of hypoxia in the progression of angiosarcoma. Methods The protein level of hypoxia inducible factor-1α (HIF-1α) in angiosarcomawas examined using immunohistochemistry and immunoblotting. To study the effect of hypoxia on tumor progression, cell proliferation, migration, invasion, and tube formation assays were performed in angiosarcomacells. The influence of tumor cell supernatant in hypoxia from angiosarcomacells on immune escape and angiogenesis was analysed to investigate the modulatory effect of hypoxia on tumor microenvironmentof angiosarcoma. The molecular mechanism related to these results was investigated using immunoblotting and real time RT-PCR. Results HIF-1α protein was over-expressed in angiosarcomatissues and cell lines under hypoxic conditions, and there was heterogeneity of oxygen supply in angiosarcoma. Hypoxia enhanced the proliferation, migration, and invasion abilities and inhibited tube formation in angiosarcomacells. Tumor cell supernatant in hypoxia from angiosarcomacells activated the monocyte invasion ability, facilitated its differentiation into M2-like macrophages, and suppressed cell-adhesion. These in vitro results were compatible to the pathological findings of angiosarcomapatients. Conclusion Hypoxia plays a major role in progression of angiosarcomacells by enhancing cell proliferation, migration, and invasion and by modulating the tumor microenvironment.