Abstract 1298: The effect of adipocyte-derived factors on lung cells: Exploring the protective nature of excess weight on lung cancer risk

Abstract

Abstract Lung cancer is the second most common cancer in men and in women (not including skin cancer) and the most common cause of cancer mortality. According to several epidemiologic papers, excess weight, identified as the BMI categories of overweight and obese, lowers lung cancer risk. Despite the numerous studies describing this anomaly, the underlying mechanisms for the protective effects are still unknown. Adipose tissue is known to secrete inflammatory molecules such as IL6, IL1β, and IL12. Activated IL6- and IL1β-associated inflammatory pathways are known to promote tumorigenesis, while the activated IL12-associated pathway inhibits tumorigenesis. We hypothesize that adipocytes create an environment that prevents lung carcinogenesis through activating inflammatory pathways that inhibit tumor growth and through blocking inflammatory pathways that promote tumor growth. To study the effect of adipocyte-derived factors on lung cells, alveolar fibroblasts (MRC5) and lung carcinoma (A549) cells were cultured in standard medium and in a 50:50 standard: adipocyte-conditioned medium (CM). In addition, cells were treated with benzo[a]pyrene (B[a]P), a known lung carcinogen. After 48 hours, mRNA expression levels of inflammatory genes were determined by RT-PCR. The data demonstrate that B[a]P treatment induced expression of IL1β, IL6 and IL12 in both cell lines. CM treatment decreased expression of IL1β and IL6 in MRC5 cells and increased their expression in A549 cells. In contrast, CM treatment decreased expression of IL12 in both cells lines. Cells treated with B[a]P plus CM had increased expression of IL12 in both cell lines, and reduced expression of IL1β and IL6 in MRC5 (2.3-fold and 6.5-fold, respectively) and A549 cells (40-fold and 11.5-fold, respectively) over B[a]P-treated cells. It was demonstrated that combined treatment increased NFκB (a transcription factor for IL1β, IL6 and IL12) mRNA expression 4-fold over control. The data suggest that conditioned medium inhibits B[a]P-induced and NFκB-mediated expression of IL1β and IL6 but increases NFκB-mediated expression IL12. This suggests that excreted factors from an adipocyte-rich environment may lead to the activation of growth-prohibiting inflammatory pathways, as opposed to growth-promoting pathways. Understanding these mechanisms and the possible discovery of biomarkers can be the foundation for new preventive techniques and treatments for lung cancer. Citation Format: Rosalind B. Penney, Daniel Sappington, Eric Siegel, Gunnar Boysen, Susan Kadlubar. The effect of adipocyte-derived factors on lung cells: Exploring the protective nature of excess weight on lung cancer risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1298. doi:10.1158/1538-7445.AM2015-1298