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Inhibition of heat shock protein 90 exerts an antitumour effect in angiosarcoma: involvement of the vascular endothelial growth factor signalling pathway
Author(s) -
YamadaKanazawa S.,
Kajihara I.,
Fukushima S.,
Jinnin M.,
Masuzawa M.,
Masuzawa M.,
Amoh Y.,
Hoshina D.,
Abe R.,
Ihn H.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15303
Subject(s) - angiosarcoma , cancer research , heat shock protein , hsp90 inhibitor , hsp90 , biology , pathology , medicine , biochemistry , gene
Summary Background Angiosarcoma is a rare malignant neoplasm derived from endothelial cells, and because advanced angiosarcoma is resistant to standard chemotherapy its prognosis is poor. Therefore, new therapies are urgently needed. Heat shock protein ( HSP )90 has been identified as a molecular chaperone that regulates various cancer‐related proteins. Numerous clinical trials are currently testing the effectiveness of HSP 90 inhibitors in various types of malignancies. Objectives To investigate the role of HSP 90 in the pathogenesis of angiosarcoma and whether the inhibition of HSP 90 may have antitumour activity. Methods The expression of HSP 90 protein in angiosarcoma was examined using immunohistochemistry and immunoblotting. The effects of HSP 90 inhibition were proven using proliferation, migration and invasion assay in angiosarcoma cells. The mechanism of antitumour effect by HSP 90 inhibition was investigated by the transfection of small interfering RNA (si RNA ). Results The levels of HSP 90 protein expression in cultured angiosarcoma cell lines were markedly increased compared with those in normal tissue cell lines. Immunohistochemical analyses revealed that the expression of HSP 90 protein was strongly detected in angiosarcoma tissues compared with that in normal dermal vessels or senile angioma tissues. Ganetespib, an HSP 90 inhibitor, with or without taxanes, inhibited the proliferation of angiosarcoma cells via apoptosis in a dose‐dependent manner. HSP 90 si RNA suppressed the proliferation, migration and invasion of angiosarcoma cells. Knock‐down of HSP 90 did not suppress vascular endothelial growth factor receptor 2 directly, but selectively suppressed several downstream targets of vascular endothelial growth factor signalling in angiosarcoma cells. Conclusions HSP 90 could be a novel therapeutic target for angiosarcoma.