Survivin: A novel marker and potential therapeutic target for human angiosarcoma.

Abstract

Human angiosarcoma is a rare malignant vascular tumor associated with extremely poor clinical outcome and generally arising in skin of the head and neck region. However, little is known about the molecular pathogeneses and useful immunohistochemical markers of angiosarcoma. To investigate the mechanisms of angiosarcoma progression, we collected 85 cases of human angiosarcoma specimens with clinical records and analyzed ISO-HAS-B patient-derived angiosarcoma cells. As control subjects, 54 cases of hemangioma and 34 of pyogenic granuloma were collected. Remarkably, consistent with our recent observations regarding the involvement of survivin expression following Hippo pathway inactivation in the neoplastic proliferation of murine hemangioendothelioma cells and human infantile hemangioma, nuclear survivin expression was observed in all cases of angiosarcoma but not in hemangiomas and pyogenic granulomas, and the Hippo pathway was inactivated in 90.3% of yes-associated protein (YAP) -positive angiosarcoma cases. However, survivin expression modes and YAP localization (Hippo pathway activation modes) were not correlated with survival. In addition, we confirmed that survivin small interference RNA (siRNA) transfection and YM155, an anti-survivin drug, elicited decreased nuclear survivin expression and cell proliferation in ISO-HAS-B cells which expressed survivin consistently. Conclusively, these findings support the importance of survivin as a good marker and critical regulator of cellular proliferation for human angiosarcoma and YM155 as a potential therapeutic agent.

• Authors: Masayuki Tsuneki, Takao Kinjo, Taisuke Mori, Akihiko Yoshida, Kayo Kuyama, Aoi Ohira, Takuya Miyagi, Kenzo Takahashi, Akira Kawai, Hirokazu Chuman, Naoya Yamazaki, Mikio Masuzawa, Hirofumi Arakawa
• Journal: Cancer science (Cancer Sci) Vol. 108 Issue 11 Pg. 2295-2305 (Nov 2017) ISSN: 1349-7006 [Electronic] England
• PMID: 28845553 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Adaptor Proteins, Signal Transducing
• BIRC5 protein, human
• Biomarkers, Tumor
• Imidazoles
• Inhibitor of Apoptosis Proteins
• Naphthoquinones
• Phosphoproteins
• Survivin
• Transcription Factors
• YAP-Signaling Proteins
• YAP1 protein, human
• Protein Serine-Threonine Kinases
• sepantronium

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Adult
• Aged
• Aged, 80 and over
• Apoptosis (drug effects)
• Biomarkers, Tumor (genetics)
• Cell Line, Tumor
• Cell Proliferation (drug effects, genetics)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Hemangiosarcoma (genetics, pathology)
• Hippo Signaling Pathway
• Humans
• Imidazoles
• Inhibitor of Apoptosis Proteins (antagonists & inhibitors, genetics)
• Male
• Middle Aged
• Naphthoquinones
• Phosphoproteins (genetics)
• Protein Serine-Threonine Kinases (genetics)
• Signal Transduction (genetics)
• Survivin
• Transcription Factors
• YAP-Signaling Proteins