American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Aug 2019
Distinct Cancer-Promoting Stromal Gene Expression Depending on Lung Function.
Rationale: Chronic obstructive pulmonary disease is an independent risk factor for lung cancer, but the underlying molecular mechanisms are unknown. We hypothesized that lung stromal cells activate pathological gene expression programs that support oncogenesis. Objectives: To identify molecular mechanisms operating in the lung stroma that support the development of lung cancer. ⋯ Furthermore, an in situ examination of lung tissue showed that stromal fibroblasts expressed cancer-associated proteins from two procancer secretomes: one that included IL-6 (in cases of mild or no airflow obstruction), and one that included BMP1 (in cases of severe airflow obstruction). Conclusions: Two distinct stromal gene expression programs that promote cancer initiation are activated in patients with lung cancer depending on lung function. Our work has implications both for screening strategies and for personalized approaches to cancer treatment.