Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis associated Lung Cancer (IPF-LC) in mice – UROP Spring Symposium 2021

Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis associated Lung Cancer (IPF-LC) in mice

Vicky Wang

UROP Logo

Pronouns: she/her

Research Mentor(s): Stefanie Galban, Assistant Professor
Research Mentor School/College/Department: Radiology, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 5 (3pm-3:50pm)
Breakout Room: Room 10
Presenter: 6

Event Link

Abstract

Lung diseases are prolific killers in the United States each year. Of the major respiratory illnesses and cancers, lung cancer (LC) and idiopathic pulmonary fibrosis (IPF) are especially notable. In the US alone, there is estimated to be 250,000 new cases of lung cancer diagnosed annually, and around 130,000 patients die from the disease as well (Cancer.org). Meanwhile, IPF affects close to 200,000 people in the United States with a 3-5 year survival rate of 50% (National Heart, Lung, and Blood Institute). For each of the two diseases, treatment options are very different, making it especially difficult to provide sufficient care. In addition, around 22% of IPF patients will go on further to develop non-small cell lung carcinoma (NSCLC), or lung cancer (The Lancet). While it is not completely clear as to why this happens, it is likely due to increased inflammation in the lungs, providing an optimal ground for tumor growth. Currently, patients who only develop lung cancer are treated with a variety of therapies such as radiation and chemotherapy. However, this won’t work for patients who have IPF and lung cancer, as the lung cancer therapies tend to exacerbate their IPF symptoms. Therefore, it is important to find a possible treatment option that will help IPF-LC patients treat their cancer without impacting their IPF in the process. In order to better understand IPF-LC’s disease progression and potentially develop new therapies to treat this pernicious disease, this study aimed to (1) recapitulate the disease progression observed in patients in a mouse model and (2) perform a comprehensive transcriptome analysis to identify gene and signaling pathway signatures that can then be targeted in future pharmacological research. Four different mouse cohorts, or experimental groups, were generated; (a) a control group, (b) a group of mice that had IPF, (c) a group of mice that had LC, and (d) a group of mice that were preconditioned with IPF and then subsequently given lung cancer cells. Bleomycin and Lewis Lung Carcinoma cells were used. Bleomycin conditions mice to develop IPF and the Lewis Lung Carcinoma metastasizes in the lungs after inoculation. Once mice developed IPF, LC or IPF-LC as assessed by micro CT and bioluminescence imaging, RNA was obtained from isolated mouse lungs, sequenced and analyzed to identify genes and signaling pathways involved. RNA analysis identified signaling pathways that were regulated in the different experimental groups. Overall, this study provided insight into the genes and signaling pathways deregulated in IPF-LC, which can then be further characterized and used to develop molecularly targeted therapies in the future.

Authors: Stefanie Galban, Vicky Wang
Research Method: Laboratory Research

lsa logoum logo