Abstract 301: Ccl17 and Ccr4 co-localize in mouse lung adenomas in vivo and are associated with epithelial cell migration in vitro

Abstract

Abstract Lung cancer is the leading cause of cancer deaths among men and women in the United States and improved treatments are urgently needed. Like many cancers, long-term inflammation is now recognized to be a contributing factor in the progression of lung cancer from a benign to a malignant state. Exactly how inflammation contributes to lung cancer is incompletely understood. Chemokines are a group of proteins that function by attracting immune cells to areas of higher chemokine concentrations. Specific chemokine-chemokine receptor pairs control the migratory response of many inflammatory cell types. It is known that chemokines and chemokine receptors can also have direct effects on cancer cells. Using in situ hybridization, we determined that the chemokine Ccl17 and its receptor Ccr4 are coordinately induced in tumor cells in transgenic and benzo(a)pyrene-induced mouse models of lung cancer. In addition, multiple subsets of T lymphocytes within mouse lung tissue express Ccr4. Immunohistochemistry localized CCR4 to cancer cells in 11 of 32 (34%) human non-small cell lung cancer biopsies while staining was not detected in 12 non-neoplastic lung biopsies. We identified human lung cancer cell lines expressing CCR4 using flow cytometry and immunofluorescence. Treatment of human NCI-H292 lung cancer cells with CCL17 peptide induced migration in a collagen-dependent manner in a transwell migration assay. The presence of Ccr4 on both lung cancer cells and lymphocytes suggests that this receptor has multiple roles in regulating lung tumor promotion and progression. Characterization of these roles may provide novel targets to inhibit lung tumor progression. Future studies will directly address the function of Ccr4 during lung tumorigenesis in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 301. doi:1538-7445.AM2012-301