Identification of the S100 fused-type protein hornerin as a regulator of tumor vascularity

Michael F. Gutknecht, Marc E. Seaman, Bo Ning, Daniel Auger Cornejo, Emily Mugler, Patrick F. Antkowiak, Christopher A. Moskaluk, Song Hu, Frederick H. Epstein, Kimberly A. Kelly*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Sustained angiogenesis is essential for the development of solid tumors and metastatic disease. Disruption of signaling pathways that govern tumor vascularity provide a potential avenue to thwart cancer progression. Through phage display-based functional proteomics, immunohistochemical analysis of human pancreatic ductal carcinoma (PDAC) specimens, and in vitro validation, we reveal that hornerin, an S100 fused-type protein, is highly expressed on pancreatic tumor endothelium in a vascular endothelial growth factor (VEGF)-independent manner. Murine-specific hornerin knockdown in PDAC xenografts results in tumor vessels with decreased radii and tortuosity. Hornerin knockdown tumors have significantly reduced leakiness, increased oxygenation, and greater apoptosis. Additionally, these tumors show a significant reduction in growth, a response that is further heightened when therapeutic inhibition of VEGF receptor 2 (VEGFR2) is utilized in combination with hornerin knockdown. These results indicate that hornerin is highly expressed in pancreatic tumor endothelium and alters tumor vessel parameters through a VEGF-independent mechanism.

Original languageEnglish
Article number552
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2017
Externally publishedYes

Fingerprint

Dive into the research topics of 'Identification of the S100 fused-type protein hornerin as a regulator of tumor vascularity'. Together they form a unique fingerprint.

Cite this