173P - Vascular endothelial growth factor-C promotes EGFR-TKIs resistance and cancer stemness via SLUG of non-small cell lung cancer

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Thoracic malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Ching-Chia Cheng
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors C. Cheng1, J. Su2
  • 1Graduate Institute Of Life Sciences, National Defense Medical Center, 114 - Taipei/TW
  • 2National Institute Of Cancer Research, National Health Research Institutes, Miaoli County/TW

Abstract

Background

Acquired resistance to the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, is a critical issue of lung cancer therapy. Vascular endothelial growth factor C (VEGF-C) promote lymphangiognesis and cancer progression but the detailed mechanism related to EGFR-TKIs resistance and cancer stemness remain mostly unclear.

Methods

The expression levels of VEGF-C and SLUG in lung cancer patients with gefitinib responder (n = 41) and gefitinib non-responder (n = 39) were examined by quantitative RT-PCR and Oncomine database analysis. The effect of VEGF-C and SLUG on EGFR-TKIs resistance by MTT assay and cancer-stem-like properties by quantitative RT-PCR in vitro.

Results

In this study, we observed that high level of VEGF-C correlated to EGFR mutation-independent gefitinib resistance and cancer-stem-like properties in vitro and in vivo; lung cancer patients with high VEGF-C expression had high level of cancer stem cell markers and worst progression-free survival. Moreover, we found a transcription factor, SLUG, involved in VEGF-C/VEGFR3-induced gefitinib resistance and cancer stemness of lung cancer.

Conclusions

These results suggest that VEGF-C is a critical role for EGFR-TKIs resistance and cancer stemness of lung cancer, and targeting VEGF-C/VEGFR3/SLUG pathway may provide a potential therapeutic strategy for lung cancer patient with acquired resistance to EGFR-TKIs.

Clinical trial identification

Legal entity responsible for the study

Jen-Liang Su

Funding

Ministry of Science and Technology, Taipei, Taiwan

Disclosure

All authors have declared no conflicts of interest.