Phenotyping of the Airway Epithelium in Search for Subpopulation of Cells Conferring Long Term Risk for Developing Lung Cancer
Conference Year
January 2019
Abstract
Lung cancer is the number one cause of cancer death; however, many patients have already quit smoking at the time of diagnosis. A critical unanswered question is, where does the risk for lung cancer reside, even after smoking cessation? Answering this question improves the understanding of tumorigenesis and aids in designing preventive strategies to individuals at greater risk. The present work examines human bronchial epithelial tissue at a single cell level using mass cytometry, a novel single-cell technology that targets proteins of interest using metal-labeled antibodies combined with mass spectrometry, providing a unique opportunity to gain insights into the cellular determinants of risk. The primary goal is to comprehensively characterize the sub-populations of airway epithelial cells that confer the greatest risk for lung cancer development. We hypothesized a subset of basal cells (BCs) known to insure progenitor cell function conferthe highest risk. The laboratory established an antibody panel to target proteins specifically expressed in subsets of human bronchial cells and compare healthy bronchial and alveolar lung tissue of individuals at low and high risk and to those with lung cancer. Once subpopulations were identified, they were flow sorted and their genomic alterations characterized by next generation sequencing for mutation burden analysis. Cancer cell lines are more proliferative based on Ki-67 expression than controls yet vary in intensity of marker staining demonstrating remarkable intra-tumor heterogeneity in proliferative response. Neuroendocrine marker, CD56, is upregulated in small cell lung cancer suggesting great inter-tumor heterogeneity. The data collected from this project will be translated to develop chemoprevention strategies targeting cell populations of interest. This study is crucial for predicting the tumor development among individuals at risk for lung cancer.
Primary Faculty Mentor Name
Sayamwong "Jom" Hammack, PhD
Secondary Mentor Name
Pierre P. Massion, MD
Status
Undergraduate
Student College
College of Arts and Sciences
Program/Major
Neuroscience
Primary Research Category
Health Sciences
Phenotyping of the Airway Epithelium in Search for Subpopulation of Cells Conferring Long Term Risk for Developing Lung Cancer
Lung cancer is the number one cause of cancer death; however, many patients have already quit smoking at the time of diagnosis. A critical unanswered question is, where does the risk for lung cancer reside, even after smoking cessation? Answering this question improves the understanding of tumorigenesis and aids in designing preventive strategies to individuals at greater risk. The present work examines human bronchial epithelial tissue at a single cell level using mass cytometry, a novel single-cell technology that targets proteins of interest using metal-labeled antibodies combined with mass spectrometry, providing a unique opportunity to gain insights into the cellular determinants of risk. The primary goal is to comprehensively characterize the sub-populations of airway epithelial cells that confer the greatest risk for lung cancer development. We hypothesized a subset of basal cells (BCs) known to insure progenitor cell function conferthe highest risk. The laboratory established an antibody panel to target proteins specifically expressed in subsets of human bronchial cells and compare healthy bronchial and alveolar lung tissue of individuals at low and high risk and to those with lung cancer. Once subpopulations were identified, they were flow sorted and their genomic alterations characterized by next generation sequencing for mutation burden analysis. Cancer cell lines are more proliferative based on Ki-67 expression than controls yet vary in intensity of marker staining demonstrating remarkable intra-tumor heterogeneity in proliferative response. Neuroendocrine marker, CD56, is upregulated in small cell lung cancer suggesting great inter-tumor heterogeneity. The data collected from this project will be translated to develop chemoprevention strategies targeting cell populations of interest. This study is crucial for predicting the tumor development among individuals at risk for lung cancer.