Adipocyte-derived exosomes promote lung cancer metastasis by increasing MMP9 activity via transferring MMP3 to lung cancer cells
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Jiaoli Wang1,*, Yilei Wu2,*, Jufeng Guo3,*, Xuefeng Fei4, Lei Yu5 and Shenglin Ma6
1Department of Respiratory Medicine, Nanjing Medical University, Affiliated Hangzhou Hospital (Hangzhou First People’s Hospital), Hangzhou, China
2Department of General Surgery, Ruian People’s Hospital, Wenzhou, China
3Department of Breast Surgery, Nanjing Medical University, Affiliated Hangzhou Hospital (Hangzhou First People’s Hospital), Hangzhou, China
4Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China
5Laboratory of Cancer Epigenetics, Department of Medical Oncology, Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Oncology, Nanjing Medical University, Affiliated Hangzhou Hospital (Hangzhou First People’s Hospital), Hangzhou, China
*These authors have contributed equally to this work
Shenglin Ma, email: [email protected]
Keywords: exosomes, adipocytes, lung cancer, MMP3, MMP9
Received: February 22, 2017 Accepted: April 12, 2017 Published: June 27, 2017
Obesity is involved in tumor progression. However, the corresponding mechanisms remain largely unknown. Here, we report that adipocytes increase the invasive ability of tumor cells by producing exosomes with a high level of MMP3. Compared with 3T3-L1 cells, 3T3-L1 adipocytes are enriched in MMP3 protein and can transfer MMP3 to 3LL lung cancer cells. Then, MMP3 activates MMP9 activity in 3LL cells and promotes invasion in vitro and in vivo via MMP9. Furthermore, MMP3 protein levels in lung tumor tissues from obese patients are increased compared with those of non-obese patients. In addition, MMP3 protein levels are positively correlated with MMP9 activity in tumor tissues. Therefore, our results reveal a novel mechanism in the adipocyte-derived exosome-mediated promotion of lung tumor metastasis, which extends our knowledge regarding obesity and tumor progression.
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