Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul, 08826, Republic of Korea.
Comparative Medicine Disease Research Center (CDRC), Science Research Center (SRC), Seoul National University, Seoul, 08826, Republic of Korea.
Exp Mol Med. 2024 Mar;56(3):734-746. doi: 10.1038/s12276-024-01181-7. Epub 2024 Mar 27.
Metastases originate from primary tumors and reach distant organs. Growing evidence suggests that metastases are under the control of primary tumors even outside the primary site; however, the mechanisms by which primary tumors remotely control metastases remain unclear. Here, we discovered a molecular mechanism by which primary tumors suppress metastatic growth. Interestingly, we found that extracellular vesicles (EVs) derived from the primary tumor can inhibit the growth of metastases both in vitro and in vivo. miR-1 was particularly enriched in primary tumor-derived EVs (pTDEs) and was found to be responsible for the suppression of metastatic growth. Mechanistically, intracellular reactive oxygen species (ROS) production and DNA damage were induced, which led to cell cycle arrest. Collectively, our data demonstrate that primary tumors restrict the growth of distant metastases via miR-1 in pTDEs and that miR-1 could potentially be used as an antimetastatic agent.
转移灶起源于原发肿瘤并到达远处器官。越来越多的证据表明，转移灶受原发肿瘤的控制，即使在原发部位之外也是如此；然而，原发肿瘤远程控制转移灶的机制尚不清楚。在这里，我们发现了一种原发肿瘤抑制转移生长的分子机制。有趣的是，我们发现来自原发肿瘤的细胞外囊泡（EVs）可以在体外和体内抑制转移的生长。miR-1 在原发肿瘤衍生的 EVs（pTDEs）中特别富集，并被发现负责抑制转移的生长。从机制上讲，细胞内活性氧（ROS）的产生和 DNA 损伤导致细胞周期停滞。总的来说，我们的数据表明，原发肿瘤通过 pTDEs 中的 miR-1 限制远处转移的生长，并且 miR-1 可能被用作抗转移剂。
