Exosomal miRNA-139 in cancer-associated fibroblasts inhibits gastric cancer progression by repressing MMP11 expression
Exosomal miRNA-139 in cancer-associated fibroblasts inhibits gastric cancer progression by repressing MMP11 expression
复制标题
癌症相关成纤维细胞中的外泌体 miRNA-139 通过抑制 MMP11 表达来抑制胃癌进展
DOI：
10.7150/ijbs.33750
复制
发表时间：
2019-01-01
影响因子：
9.2
通讯作者：
Zhang, Weijie
中科院分区：
文献类型：
--
作者：
Xu, Guifang;Zhang, Bin;Zhang, Weijie
实体瘤除癌细胞外还包含各种类型的基质细胞。癌症相关成纤维细胞（CAF）是肿瘤基质的主要组成部分，在包括胃癌在内的多种恶性肿瘤的肿瘤进展和转移中发挥着重要作用。然而，CAFs对胃癌细胞进展和转移的影响尚未得到充分研究。在这里，我们发现 CAF 分泌的外泌体中的基质金属蛋白酶 11 (MMP11) 可以被递送到胃癌细胞中。胃癌 CAF 部分通过外泌体 MMP11 促进胃癌细胞迁移。此外，MMP11在从胃癌患者血浆和肿瘤组织中纯化的外泌体中过度表达，并且与胃癌患者的总生存期相关。我们还发现胃癌 CAF 中 MMP11 受到外泌体 miR-139 的负调控。外泌体 miR-139 通过降低体外和体内 MMP11 的表达来抑制胃癌细胞的肿瘤生长和转移。因此，我们提出源自胃CAF的外泌体miR-139可以通过减少肿瘤微环境中的MMP11来抑制胃癌的进展和转移。
Solid tumors consist of various types of stromal cells in addition to cancer cells. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and play an essential role in tumor progression and metastasis in a variety of malignancies, including gastric cancer. However, the effects of CAFs on gastric cancer cells' progression and metastasis are not well studied. Here we show that matrix metalloproteinase 11 (MMP11) in exosomes secreted from CAFs can be delivered into gastric cancer cells. Gastric CAFs promote gastric cancer cell migration partially through exosomal MMP11. Moreover, MMP11 is overexpressed in exosomes purified from plasma of gastric cancer patients and tumor tissues and associated with overall survival of gastric patients. We also find that MMP11 is negatively regulated by exosomal miR-139 in the CAFs of gastric cancer. Exosomal miR-139 inhibits tumor growth and metastasis of gastric cancer cells by decreasing the expression of MMP11 in vitro and in vivo. Thus, we propose that exosomal miR-139 derived from gastric CAFs could inhibit the progression and metastasis of gastric cancer by decreasing MMP11 in tumor microenvironment.