Adipose-Derived Stem Cells Enhance Cancer Stem Cell Property and Tumor Formation Capacity in Lewis Lung Carcinoma Cells Through an Interleukin-6 Paracrine Circuit.
Adipose-derived stem cells (ADSCs) are multipotent cells that have attracted much recent attention and emerged as therapeutic approaches in several medical fields. Although current knowledge of the biological impacts of ADSCs in cancer research is greatly improved, the underlying effects of ADSCs in tumor development remain controversial and cause the safety concerns in clinical utilization. Hence, we isolated primary ADSCs from the abdominal fat of mice and conducted interaction of ADSCs with Lewis lung carcinoma cells in culture and in mice to investigate the impacts of ADSCs on tumor development. Cytokine array and neutralizing antibody were further utilized to identify the key regulator and downstream signaling pathway. In this study, we demonstrated that ADSCs enhance the malignant characteristics of LLC1 cells, including cell growth ability and especially cancer stem cell property. ADSCs were then identified to promote tumor formation and growth in mice. We further determined that ADSC interaction with LLC1 cells stimulates increased secretion of interleukin-6 mainly from ADSCs, which then act in a paracrine manner on LLC1 cells to enhance their malignant characteristics. Interleukin-6 was also identified to regulate genes related to cell proliferation and cancer stem cell, as well as to activate JAK2/STAT3, a predominant interleukin-6-activated pathway, in LLC1 cells. Collectively, we demonstrated that ADSCs play a pro-malignant role in tumor development of Lewis lung carcinoma cells by particularly promoting cancer stem cell property through interleukin-6 paracrine circuit, which is important for safety considerations regarding the clinical application of ADSCs.
1 Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University , Taipei City, Taiwan .
Jui-Hua
JH
Lu
1 Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University , Taipei City, Taiwan .|2 Stem Cell Research Center, Taipei Medical University , Taipei City, Taiwan .
Hong-Jian
HJ
Wei
3 Department of Dentistry, Taipei Medical University Hospital , Taipei City, Taiwan .|4 School of Dentistry, College of Oral Medicine, Taipei Medical University , Taipei City, Taiwan .
Bou-Yue
BY
Peng
4 School of Dentistry, College of Oral Medicine, Taipei Medical University , Taipei City, Taiwan .
Hsin-Hua
HH
Chou
2 Stem Cell Research Center, Taipei Medical University , Taipei City, Taiwan .
Wei-Hong
WH
Chen
2 Stem Cell Research Center, Taipei Medical University , Taipei City, Taiwan .
Hen-Yu
HY
Liu
1 Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University , Taipei City, Taiwan .|2 Stem Cell Research Center, Taipei Medical University , Taipei City, Taiwan .|5 College of Medicine, Fu Jen Catholic University , New Taipei City, Taiwan .
Win-Ping
WP
Deng
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D019899:Paracrine Communication; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2
adipose-derived stem cell; cancer stem cells; interleukin-6; lung cancer