Liu Doudou, Li Xiaoshuang, Zeng Bin, Zhao Qiting, Chen Hao, Zhang Yuhan, Chen Yuting, Wang Jianyu, Xing H Rosie
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China.
Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China.
Stem Cell Rev Rep. 2023 Jan;19(1):155-169. doi: 10.1007/s12015-022-10358-4. Epub 2022 Mar 17.
High mortality rate and poor survival in melanoma are associated with efficient metastatic colonization. The underlying mechanisms remain elusive. Elucidating the role of exosomes in mediating the interactions between cancer cells and the metastatic microenvironment has been focused on cancer cell derived exosomes in modulating the functions of stromal cells. Whether cancer stem cells (CSCs) can modify the metastatic properties of non-CSC cells, and whether exosomal crosstalk plays a role have not been demonstrated prior to this report. In this study, a paired M14 melanoma derivative cell line, i.e., melanoma parental cell (MPC) and its CSC derivative cell line melanoma stem cell (MSC) were employed. We demonstrated that exosomal crosstalk betwen MSCs and non-CSC MPCs is a new mechanism that underlies melanoma metastasis. Low metastatic melanoma cells (MPCs) can acquire the "metastatic power" from highly metastatic melanoma CSCs (MSCs). We illustrated an uncharacterized microRNA, miR-4535 in mediating such exosomal crosstalk. MSCs deliver its exosomal miR-4535 to the targeted MPCs. Upon entering MPCs, miR-4535 augments metastatic colonization of MPCs by inactivating the autophagy pathway.
黑色素瘤的高死亡率和低生存率与有效的转移定植有关。其潜在机制仍不清楚。阐明外泌体在介导癌细胞与转移微环境之间相互作用中的作用一直聚焦于癌细胞来源的外泌体对基质细胞功能的调节。在此报告之前，癌症干细胞（CSCs）是否能改变非CSC细胞的转移特性以及外泌体串扰是否起作用尚未得到证实。在本研究中，使用了一对M14黑色素瘤衍生细胞系，即黑色素瘤亲本细胞（MPC）及其CSC衍生细胞系黑色素瘤干细胞（MSC）。我们证明，MSC与非CSC MPC之间的外泌体串扰是黑色素瘤转移的一种新机制。低转移黑色素瘤细胞（MPC）可以从高转移黑色素瘤CSC（MSC）获得“转移能力”。我们阐明了一种未表征的微小RNA，即miR-4535在介导这种外泌体串扰中的作用。MSC将其外泌体miR-4535递送至靶向的MPC。进入MPC后，miR-4535通过使自噬途径失活增强MPC的转移定植。
