Oncotarget

Research Papers:

FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells

Hong-Jian Wei _, Wen-Cheng Lo, Jac A. Nickoloff, Wei-Hong Chen, Hen-Yu Liu, Ya-Ting Chang, Pan-Chyr Yang, Cheng-Wen Wu, David F. Williams, Juri G. Gelovani and Win-Ping Deng

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Oncotarget. 2014; 5:9514-9529. https://doi.org/10.18632/oncotarget.2413

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Abstract

Hong-Jian Wei1,2, Jac A. Nickoloff3, Wei-Hong Chen2, Hen-Yu Liu2, Wen-Cheng Lo4,5, Ya-Ting Chang1, Pan-Chyr Yang6, Cheng-Wen Wu7, David F. Williams8, Juri G. Gelovani9,10, Win-Ping Deng1,2

1Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan

2Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan

3Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA

4Department of Neurosurgery, Taipei Medical University Hospital, Taipei 110, Taiwan

5School of Medicine, Taipei Medical University, Taipei 110, Taiwan

6Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan

7Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 112, Taiwan

8Wake Forest Institute of Regenerative Medicine, Winston-Salem, NC 27157, USA

9Department of Biomedical Engineering, College of Engineering and School of Medicine, Wayne State University, Detroit, MI 48201, USA

10Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA

Correspondence to:

Win-Ping Deng, e-mail: [email protected]

Keywords: cell fusion; mesenchymal stem cell; lung cancer cell; reprogramming; FOXF1; p21

Received: June 26, 2014     Accepted: August 28, 2014     Published: September 06, 2014

ABSTRACT

Several reports suggest that malignant cells generate phenotypic diversity through fusion with various types of stromal cells within the tumor microenvironment. Mesenchymal stem cell (MSC) is one of the critical components in the tumor microenvironment and a promising fusogenic candidate, but the underlying functions of MSC fusion with malignant cell have not been fully examined. Here, we demonstrate that MSCs fuse spontaneously with lung cancer cells, and the latter is reprogrammed to slow growth and stem-like state. Transcriptome profiles reveal that lung cancer cells are reprogrammed to a more benign state upon MSC fusion. We further identified FOXF1 as a reprogramming mediator that contributes not only to the reprogramming toward stemness but also to the p21-regulated growth suppression in fusion progeny. Collectively, MSC fusion does not enhance the intrinsic malignancy of lung cancer cells. The anti-malignant effects of MSC fusion-induced reprogramming on lung cancer cells were accomplished by complementation of tumorigenic defects, including restoration of p21 function and normal terminal differentiation pathways as well as up-regulation of FOXF1, a putative tumor suppressor. Such fusion process raises the therapeutic potential that MSC fusion can be utilized to reverse cellular phenotypes in cancer.


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