In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1594-1594
Abstract:
The tumor microenvironment and its immune components play a critical role in cancer development, progression, and control. In this study we aim to investigate the role of tumor infiltrating lymphocyte subpopulations in lung cancer progression. Conditioned media (CM) from co-cultures of human lymphocytes with adenocarcinoma cells (A549) induced the loss of the epithelial markers (E-Cadherin and ZO2 and an increase of mesenchymal markers (vimentin, N-cadherin on mRNA and protein level. In addition, the cells demonstrated a spindled shape-like morphological changes and an increased migratory property. In order to explore the molecular mechanism that led to lymphocyte-induced EMT and migration, we performed a cytokine array from the co-culture CM and found elevated levels of IL-8, IL-16, CCL2 and G-CSF. Furthermore, we observed that lymphocyte-induced EMT was mediated via a TGFβ-independent pathway that involves phosphorylation of ERK1/2. Notably, this EMT phenotype induction by lymphocytes was independent of the pre-activation of lymphocytes with PMA. Furthermore, in order to identify the specific CD4+ T cell subpopulations (Th0, Th1, Th9 and Th17) responsible for the EMT effect, we generated specific subpopulations from mouse spleen T cells. Interestingly, we observed that Th9 and Th17 subpopulation CM led to EMT and increased migratory phenotype in mouse lung cancer cell lines. Additionally, we identified the T lymphocyte secretory cytokine, IL9, as responsible for the Th9 induced EMT and migratory phenotype of lung cancer cells. This study reveals that specific T lymphocyte subpopulations, i.e. Th9 and Th17 induce EMT in lung cancer cells, suggesting T cell regulated mechanisms of metastasis. Citation Format: Ylia Salazar, Magdalena Huber, Anja Schmall, Werner Seeger, SoniSavai Pullamsetti, Rajkumar Savai, Magdalena Huber, Anja Schmall, Werner Seeger, SoniSavai Pullamsetti. Contribution of Stromal Lymphocytes to Lung Cancer Metastasis: Role in Epithelial Mesenchymal Transition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1594.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2016-1594
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
