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

Cancer Sci. 2017 Nov;108(11):2295-2305. doi: 10.1111/cas.13379. Epub 2017 Sep 15.

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.

Keywords: Angiosarcoma; Hippo pathway; YM155; proliferation; survivin.

MeSH terms

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

Substances

  • 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