Zhao Qiting, Chen Hao, Li Xiaoshuang, Zeng Bin, Sun Zhiwei, Liu Doudou, Chen Yuting, Zhang Yuhan, Rosie Xing H, Wang Jianyu
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.
Cell Death Discov. 2022 Apr 9;8(1):188. doi: 10.1038/s41420-022-00993-8.
The mean survival of metastatic melanoma is less than 1 year. While the high mortality rate is associated with the efficient metastatic colonization of the involved organs, the underlying mechanisms remain elusive. The role of exosomes in facilitating the interactions between cancer cells and the metastatic microenvironment has received increasing attention. Previous studies on the role of exosomes in metastasis have been heavily focused on cancer cell-derived exosomes in modulating the functions of stromal cells. Whether the extravasated neighboring cancer cells at the distant organ can alter the metastatic properties of one another, a new mechanism of metastatic colonization, has not been demonstrated prior to this report. In this study, a paired M4 melanoma derivative cell lines, i.e., M14-OL and POL, that we established and characterized were employed. They exhibit high (POL cells) and low (OL cells) metastatic colonization efficiency in vivo, respectively. We show that exosomal crosstalk between metastatic cancer cells is a new mechanism that underlies cancer metastasis and heterogeneity. Low metastatic melanoma cells (OL) can acquire the "metastatic power" from highly metastatic melanoma cells (POL). POL achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-199a-1-5p, to the targeted OL cell which in turn inactivates cell cycle inhibitor CDKN1B and augments metastatic colonization.
转移性黑色素瘤的平均生存期不到1年。虽然高死亡率与受累器官的有效转移性定植有关，但其潜在机制仍不清楚。外泌体在促进癌细胞与转移微环境之间相互作用中的作用越来越受到关注。先前关于外泌体在转移中作用的研究主要集中在癌细胞衍生的外泌体对基质细胞功能的调节上。在本报告之前，尚未证实远处器官中渗出的邻近癌细胞是否能相互改变转移特性，这是一种新的转移定植机制。在本研究中，我们使用了我们建立并表征的一对M4黑色素瘤衍生细胞系，即M14-OL和POL。它们在体内分别表现出高（POL细胞）和低（OL细胞）转移定植效率。我们表明，转移性癌细胞之间的外泌体串扰是癌症转移和异质性的一种新机制。低转移性黑色素瘤细胞（OL）可以从高转移性黑色素瘤细胞（POL）获得“转移能力”。POL通过利用其外泌体将功能性miRNA（如miR-199a-1-5p）传递给靶向的OL细胞来实现这一目标，而OL细胞反过来会使细胞周期抑制剂CDKN1B失活并增强转移定植。
