Abstract
Background: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete-scute family bHLH transcription factor 1 (ASCL1). By analyzing transcriptome data, we reported that ASCL1 plays a tumor-promoting role and ASCL1-high lung adenocarcinoma exhibits poor immune responses; however, its mechanism is largely unknown.
Method: ASCL1 was retrovirally transduced in two different mouse lung adenocarcinoma cell lines (LLC and CMT64 cells). Expression profiles of soluble factors in the cell culture media were tested by antibody arrays designed to detect 111 different cytokines, chemokines and growth factors. The effect of ASCL1 expression on tumorigenesis was studied by a syngenic orthotropic model of LLC cells. Immune cell infiltration in the grafted tumors was evaluated by immunohistochemistry.
Result: ASCL1 transduction in mouse lung adenocarcinoma cells was confirmed by immunoblotting. Neuroendocrine markers were upregulated by ectopic ASCL1. Cell proliferation was increased by ASCL1 expression in both cell lines. Intrapulmonary injection of LLC cells resulted in enhanced tumor growth by ASCL1. Two independent experiments of antibody arrays were performed in two different cell lines. CCL20 and MMP-3 were consistently downregulated by ectopic ASCL1. Immunostaining for immune cell markers indicated that immune cell infiltration was altered in ASCL1-expressing grafted tumors.
Conclusion: ASCL1 expression promotes tumorigenesis in lung adenocarcinoma and is associated with a characteristic immune response, at least partly due to an altered expression pattern of soluble factors such as CCL20.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA3668.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019