Our goal is to understand how cancer-associated fibroblasts (CAFs) drive the malignant progression of lung cancer by functioning as pericytes. We use cell co-culture systems in which CAFs exhibit pericytic properties, secrete a collagen-rich matrix, and communicate bi-directionally with tumor cells, endothelial cells, and macrophages to create vessels and regulate tumor cell migration and invasion. These cells are derived from genetically-engineered mice that express vascular reporters and develop lung adenocarcinoma that are highly fibrotic and infiltrated by CAFs that produce collagen and a plethora of pro-inflammatory and pro-angiogenic cytokines. For validation studies, we use a large bank of human lung cancers annotated for somatic oncogenic mutations and clinical variables. This is a highly collaborative project with a multi-disciplinary group of investigators at MD Anderson Cancer Center, Baylor College of Medicine, and Rice University who are funded by NIH and other agencies to address this question.
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