Abstract 5064: EGFR and HER3 are important in the interaction between lung cancer cells and fibroblasts

Abstract

Abstract Introduction: The cancer microenvironment has been recognised as a major factor in the development and treatment of lung cancer. Fibroblasts have gained attention owing to their ability to stimulate the growth of cancer cells and to change the response to chemotherapy. Though, not much is known about the underlying mechanisms. Methods: Lung cancer cell lines (H1568, Calu-3 and HCC827) and a lung fibroblast cell line (WI-38) were grown in co-culture using a Boyden chamber assay. Results: The presence of lung fibroblasts markedly increased growth of the lung cancer cells during co-culture. We investigated the activation of 49 different receptor tyrosine kinases and found that H1568 activated only EGFR and HER3. Activation of EGFR and HER3 was confirmed in Calu-3 and HCC827 after co-culture with fibroblasts. To account for this activation, we measured the expression of all EGFR ligands in the cell lines. We found that all lung cancer cell lines had increased levels of amphiregulin mRNA after co-culture with fibroblasts. ELISA confirmed increased protein production. We also found that the amount of available amphiregulin in the media of the co-culture is increased compared to controls. Conclusion: Lung fibroblasts stimulate the growth of lung cancer cells lines. We suggest that this effect is obtained by activation of EGFR and HER3. Furthermore we show that co-culture induce increased amphiregulin production in the cancer cells. This study identifies EGFR and HER3 as important components in the interaction between lung cancer cells and fibroblasts. Citation Format: Christina Demuth, Kristine Raaby Jakobsen, Peter Meldgaard, Anders Lade Nielsen, Boe Sandahl Sorensen. EGFR and HER3 are important in the interaction between lung cancer cells and fibroblasts. [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 5064. doi:10.1158/1538-7445.AM2015-5064