206P - Hypoxia-induced cell stemness leads to drug resistance and poor prognosis in lung adenocarcinoma

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Mingchuan Zhao
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors M. Zhao1, Y. Zhang2, X. Chen3, C. Zhou2, G. Liu3, X. Chen4
  • 1Medical Oncology, Shanghai Pulmonary Hospital, 200433 - Shanghai/CN
  • 2Medical Oncology, Shanghai Pulmonary Hospital, Shanghai/CN
  • 3Translational Medical Center, Shanghai Pulmonary Hospital, Shanghai/CN
  • 4Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai/CN

Abstract

Aim

We aimed to prove that hypoxia may lead to an increasing number of cancer stem cells or cancer cell stemness. Therefore, targeting of a stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer.

Methods

We used cobalt dichloride (CoCl2) to create a hypoxic environment for the lung adenocarcinoma cell line A549 and its cisplatin-resistant cell line A549/DDP. The change in cell stemness was detected by quantitative real-time PCR and drug resistance was measured by determining the IC50 value. The cancer stem-like cell population of the cell-line was detected by flowcytometry and separated by magnetic antibodies which recognized the cancer stemness marker CD166. A cultured stem-like cell population was compared with other cells not expressing the stem cell marker using proliferation assay and IC50 values. Finally, a tissue array was used to analyze the relationship between hypoxia-induced stemness and overall survival after radical surgery.

Results

Chemical-induced hypoxia changed cell stemness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance, such as cisplatin, docetaxel and pemetrexed. The CD166-positive cancer stem cell-like population showed greater drug resistance compared to CD166-negativecells. Tissue array also showed poorer prognosis for patients whose tissues expressed higher levels of CD166.

Conclusions

Our findings indicate that chemical hypoxia may augment cancer cell stemness and drug resistance in CD166-positive stem cells. Moreover, CD166 expression may be a key marker in the monitoring and clinical management of multiple cancer therapies.

Disclosure

All authors have declared no conflicts of interest.