Bacillus anthracis Protective Antigen Shows High Specificity for a UV Induced Mouse Model of Cutaneous Squamous Cell Carcinoma

Frontiers in Medicine
Theo CrawfordYasvir Tesiram

Abstract

Squamous cell carcinoma (SCC) accounts for the majority of non-melanoma skin cancer related deaths, particularly in immunosuppressed persons. Identification of biomarkers that could be used to identify or treat SCC would be of significant benefit. The anthrax toxin receptors, Tumor Endothelial Marker 8 (TEM8) and Capillary Morphogenesis Gene 2 (CMG2), are endothelial receptors involved in extracellular matrix homeostasis and angiogenesis that are selectively upregulated on numerous tumors. One method of targeting these receptors is Protective Antigen (PA), a protein produced by B. anthracis that mediates binding and translocation of anthrax toxins into cells. PA targeted toxins have been demonstrated to selectively inhibit tumor growth and angiogenesis, but tumor selectivity of PA is currently unknown. In this work fluorescently labeled PA was shown to maintain receptor dependent binding and internalization in vitro. Utilizing a human papillomavirus transgenic mouse model that develops cutaneous SCC in response to ultraviolet irradiation we identified tumor uptake of PA in vivo. The intravenously administered PA resulted in tumor specific localization, with exclusive tumor detection 24 h post injection. Ex vivo analysis identif...Continue Reading

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Methods Mentioned

BETA
transgenic
affinity purification
size exclusion chromatography
X-ray
fluorescence optical imaging
light scattering
surgical resection

Software Mentioned

Bruker Multispectral
GraphPad Prism
ImageJ
FV10
Image J FIJI
NIS elements

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