Adipocyte-derived exosomes promote lung cancer metastasis by increasing MMP9 activity via transferring MMP3 to lung cancer cells

脂肪细胞衍生的外泌体通过将 MMP3 转移到肺癌细胞中来增加 MMP9 活性,从而促进肺癌转移

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作者:Jiaoli Wang, Yilei Wu, Jufeng Guo, Xuefeng Fei, Lei Yu, Shenglin Ma

Abstract

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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