Oncotarget

Research Papers:

CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling

Wei-Liang Chen, Ai-Fang Huang, Shih-Ming Huang, Ching-Liang Ho, Yung-Lung Chang and James Yi-Hsin Chan _

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Oncotarget. 2017; 8:54115-54135. https://doi.org/10.18632/oncotarget.11132

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Abstract

Wei-Liang Chen1,2,3, Ai-Fang Huang1, Shih-Ming Huang1,4, Ching-Liang Ho5, Yung-Lung Chang4 and James Yi-Hsin Chan1,6,7

1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan, Republic of China

2Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, and School of Medicine, National Defense Medical Center, Taipei 114, Taiwan, Republic of China

3Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, and School of Medicine, National Defense Medical Center, Taipei 114, Taiwan, Republic of China

4Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, Republic of China

5Division of Hematology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, Republic of China

6Department of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan, Republic of China

7Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, Republic of China

Correspondence to:

James Yi-Hsin Chan, email: jchan9473@gmail.com

Keywords: CD164, lung cancer, tumorigenesis, cancer stem cell, drug resistance

Received: May 11, 2016     Accepted: July 28, 2016     Published: August 9, 2016

ABSTRACT

CD164 is a cell adhesion molecule that increases hematopoietic stem cell proliferation, adhesion, and migration via C-X-C chemokine receptor type 4 (CXCR4) signaling. Emerging evidence indicates that elevated CD164 expression is associated with aggressive metastasis, advanced stages, and shorter overall survival in lung cancer. However, no data are available regarding the clinical significance of CD164 expression in lung cancer. This study explores whether CD164 promotes tumor-initiation and drug resistance through the stem cell property. Using tissue microarrays, we determine that CD164 expression is correlated with clinicopathological characteristics in human lung cancer. The CD164 overexpression in normal lung epithelial cells (BEAS2B cells) leads to malignant transformation in vitro, tumorigenicity in xenografted mice, stem cell-like property, and drug resistance through ATP-binding cassette transporters. The CD164 overexpression increases CXCR4 expression and activates Akt/mTOR signaling. Rapamycin, an mTOR inhibitor, hinders cell proliferation along with sphere formation in vitro and impedes tumor growth in vivo. In conclusion, we have provided evidence that CD164 promotes the growth of lung tumor-initiating cells with stem cell properties and induces tumor growth and drug resistance through Akt/mTOR signaling. Therefore, identification of CD164 as a cancer stem cell therapeutic marker may develop an effective therapy in patients with chemoresistant lung cancer.


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