Skip to Content
Merck
  • Identification of the S100 fused-type protein hornerin as a regulator of tumor vascularity.

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

Nature communications (2017-09-17)
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
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.Angiogenesis is essential for solid tumor progression. Here, the authors interrogate the proteome of pancreatic cancer endothelium via phage display and identify hornerin as a critical protein whose expression is essential to maintain the pancreatic cancer vasculature through a VEGF-independent mechanism.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-HRNR antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Hrnr
Sigma-Aldrich
Anti-Actin, α-Smooth Muscle - Cy3 antibody, Mouse monoclonal, clone 1A4, purified from hybridoma cell culture