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

Abstract

BACKGROUND:

Since cancer stem cells exhibit embryonic-like self-renewal characteristics and malignant behavior, including drug resistance and metastasis, they may be the origin of tumorigenesis and cancer recurrence. Cancer cell stemness is also highly relevant to cancer in hypoxic environments.

METHODS:

In our study, we used cobalt dichloride (CoCl2) to create a hypoxic environment for lung adenocarcinoma A549 cells and the cisplatine-resistant cell line A549/DDP. The cancer stem-like CD166 positive population and the cells' stemness were detected by flowcytometry and quantitative real-time PCR after separation using magnetic antibodies. Drug resistance to cisplatine, docetaxel and pemetrexed was also measured. Finally, a tissue array was used to analyze the relationship between hypoxia-induced stemness and overall survival after radical surgery.

RESULTS:

Data showed that chemical-induced hypoxia changed cell stemness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance. The CD166-positive cancer stem cell-like population showed greater drug resistance than the CD166-negative cells. Tissue array studies also suggested a poorer prognosis for patients whose tissue expressed higher CD166 levels.

CONCLUSION:

Our findings indicate that chemical hypoxia may augment cancer cell stemness and drug resistance in CD166-positive stem cells. Therefore, targeting the stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer.

• Authors: Mingchuan Zhao, Yishi Zhang, Huijun Zhang, Shaohua Wang, Mengmeng Zhang, Xi Chen, Heyong Wang, Gang Zeng, Xiaofeng Chen, Gentao Liu, Caicun Zhou
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 87 Issue 2 Pg. 98-106 (Feb 2015) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 25512094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Activated-Leukocyte Cell Adhesion Molecule
• Antineoplastic Agents
• Biomarkers
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger

Topics

• Activated-Leukocyte Cell Adhesion Molecule (genetics, metabolism)
• Adenocarcinoma (genetics, metabolism, mortality, pathology)
• Adenocarcinoma of Lung
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (pharmacology)
• Biomarkers
• Cell Hypoxia (genetics)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm (genetics)
• Female
• Gene Expression
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Immunophenotyping
• Lung Neoplasms (genetics, metabolism, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Neoplastic Stem Cells (metabolism)
• Prognosis
• RNA, Messenger (genetics, metabolism)
• Survival Analysis
• Young Adult