Superfund Research Program
Arsenic-Induced Pseudohypoxia Drives Malignant Transformation in Lung Cancer
Project Leader: Walter T. Klimecki
Grant Number: P42ES004940
Funding Period: 2010-2017
Final Progress Reports
Year: 2016 2014
Studies in this project were aimed at understanding the changes in energy metabolism caused by environmentally relevant concentrations (1 uM) of arsenic in lung epithelial cell lines. Researchers are using human-derived lung epithelial cell lines to model the cells that are likely targeted for lung cancer transformation-one of the public health impacts of chronic arsenic exposure. The research team’s work suggests that arsenic-induced changes in energy metabolism are associated with loss of cell identity as an epithelial cell, and gain of cell identify as mesenchymal. This so-called epithelial to mesenchymal transformation (EMT) is one of the hallmarks of cancer development. One of the exciting leads that this team has worked on is within the same cell line (called BEAS-2B). Cells that undergo EMT, even though they are genetically identical to cells that have not undergone EMT, are substantially more sensitive to toxicity caused by arsenic. Researchers think that this is important because lung lining cells can undergo EMT normally as part of the process of healing a small injury to the lung lining, something that happens as a part of normal living. If, however, one of these attempts to heal a defect by undergoing EMT occurs in an arsenic-exposed individual, those EMT-transformed cells might be more sensitive to arsenic’s effects. Because EMT-transformed cells are normally only temporarily closer in behavior to cancer cells, they may be more susceptible to cancerous transformation induced by arsenic.