Liu Zhixiao, Jin Qishu, Yan Taofei, Wo Yinqing, Liu Huiwen, Wang Yue
Research Center of Developmental Biology, Department of Histology and Embryology, College of Basic Medicine, Naval Medical University, Shanghai, 200433, China.
The Department of Histology and Embryology, Harbin Medical University, Harbin, 150086, China.
Biochem Biophys Rep. 2022 Jul 2;31:101299. doi: 10.1016/j.bbrep.2022.101299. eCollection 2022 Sep.
Physical cues in the extracellular microenvironment regulate cancer cell metastasis. Functional microRNA (miRNA) carried by cancer derived exosomes play a critical role in extracellular communication between cells and the extracellular microenvironment. However, little is known about the role of exosomes loaded miRNAs in the mechanical force transmission between cancer cells and extracellular microenvironment. Herein, our results suggest that stiff extracellular matrix (ECM) induced exosomes promote cancer cell migration. The ECM mechanical force regulated the exosome miRNA cargo of prostate cancer cells. Exosome miRNAs regulated by the ECM mechanical force modulated cancer cell metastasis by regulating cell motility, ECM remodeling and the interaction between cancer cells and nerves. Focal adhesion kinase mediated-ECM mechanical force regulated the intracellular miRNA expression, and F-actin mediate-ECM mechanical force regulated miRNA packaging into exosomes. The above results demonstrated that the exosome miRNA cargo promoted cancer metastasis by transmitting the ECM mechanical force. The ECM mechanical force may play multiple roles in maintaining the microenvironment of cancer metastasis through the exosome miRNA cargo.
细胞外微环境中的物理线索调节癌细胞转移。癌症衍生的外泌体携带的功能性微小RNA（miRNA）在细胞与细胞外微环境之间的细胞外通讯中起关键作用。然而，关于负载miRNA的外泌体在癌细胞与细胞外微环境之间的机械力传递中的作用知之甚少。在此，我们的结果表明，坚硬的细胞外基质（ECM）诱导的外泌体促进癌细胞迁移。ECM机械力调节前列腺癌细胞的外泌体miRNA负载。由ECM机械力调节的外泌体miRNA通过调节细胞运动性、ECM重塑以及癌细胞与神经之间的相互作用来调节癌细胞转移。粘着斑激酶介导的ECM机械力调节细胞内miRNA表达，而F-肌动蛋白介导的ECM机械力调节miRNA包装到外泌体中。上述结果表明，外泌体miRNA负载通过传递ECM机械力促进癌症转移。ECM机械力可能通过外泌体miRNA负载在维持癌症转移微环境中发挥多种作用。
