Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
WPI Nano Life Science Institute, Kanazawa University, Kanazawa, Japan.
Nat Commun. 2021 Feb 8;12(1):863. doi: 10.1038/s41467-021-21160-0.
A concept of polyclonal metastasis has recently been proposed, wherein tumor cell clusters break off from the primary site and are disseminated. However, the involvement of driver mutations in such polyclonal mechanism is not fully understood. Here, we show that non-metastatic AP cells metastasize to the liver with metastatic AKTP cells after co-transplantation to the spleen. Furthermore, AKTP cell depletion after the development of metastases results in the continuous proliferation of the remaining AP cells, indicating a role of AKTP cells in the early step of polyclonal metastasis. Importantly, AKTP cells, but not AP cells, induce fibrotic niche generation when arrested in the sinusoid, and such fibrotic microenvironment promotes the colonization of AP cells. These results indicate that non-metastatic cells can metastasize via the polyclonal metastasis mechanism using the fibrotic niche induced by malignant cells. Thus, targeting the fibrotic niche is an effective strategy for halting polyclonal metastasis.
最近提出了多克隆转移的概念，其中肿瘤细胞簇从原发部位脱落并扩散。然而，在这种多克隆机制中驱动突变的参与尚不完全清楚。在这里，我们显示在共同移植到脾脏后，非转移性 AP 细胞与转移性 AKTP 细胞一起转移到肝脏。此外，转移发生后 AKTP 细胞耗竭导致剩余的 AP 细胞持续增殖，表明 AKTP 细胞在多克隆转移的早期步骤中起作用。重要的是，AKTP 细胞而非 AP 细胞在窦内停滞时诱导纤维性龛生成，并且这种纤维性微环境促进 AP 细胞的定植。这些结果表明，非转移性细胞可以通过恶性细胞诱导的纤维性龛，通过多克隆转移机制转移。因此，靶向纤维性龛是阻止多克隆转移的有效策略。
