Data from Precision Cut Lung Slices as a Preclinical Model for Non–Small Cell Lung Cancer Chemoprevention

Abstract

<div>Abstract<p>Lung cancer chemoprevention is critical to addressing cancer burden in high-risk populations. Chemoprevention clinical trials rely on data from preclinical models; however, <i>in vivo</i> studies have high financial, technical, and staffing requirements. Precision cut lung slices (PCLS) provide an <i>ex vivo</i> model that maintains the structure and function of native tissues. This model can be used for mechanistic investigations and drug screenings and reduces the number of animals and time required to test hypotheses compared with <i>in vivo</i> studies. We tested the use of PCLS for chemoprevention studies, demonstrating recapitulation of <i>in vivo</i> models. Treatment of PCLS with the PPARγ agonizing chemoprevention agent iloprost produced similar effects on gene expression and downstream signaling as <i>in vivo</i> models. This occurred in both wild-type tissue and Frizzled 9 knockout tissue, a transmembrane receptor required for iloprost's preventive activity. We explored new areas of iloprost mechanisms by measuring immune and inflammation markers in PCLS tissue and media, and immune cell presence with immunofluorescence. To demonstrate the potential for drug screening, we treated PCLS with additional lung cancer chemoprevention agents and confirmed activity markers in culture. PCLS offers an intermediate step for chemoprevention research between <i>in vitro</i> and <i>in vivo</i> models that can facilitate drug screening prior to <i>in vivo</i> studies and support mechanistic studies with more relevant tissue environments and functions than <i>in vitro</i> models.</p>Prevention Relevance:<p>PCLS could be a new model for premalignancy and chemoprevention research, and this work evaluates the model with tissue from prevention-relevant genetic and carcinogen exposed <i>in vivo</i> mouse models, in addition to evaluating chemoprevention agents.</p></div>