Zhang Jian, Wu Jiangmei
Institute of Laboratory Animal Science, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Front Oncol. 2021 Feb 5;10:611054. doi: 10.3389/fonc.2020.611054. eCollection 2020.
Bone metastasis is closely related to the alterations of bone microenvironment. In this article, we hypothesize that exosomes may be involved in the "vicious circle" by transferring miR-214. miR-214 is highly expressed in lung adenocarcinoma, and is closely related to the degree of lung cancer progression. As a key regulator of bone homeostasis, miR-214 promotes osteoclast differentiation and mediates intercellular communication between osteoclasts and osteoblasts the way of exosomal miRNA. Therefore, it is highly probable that exosomal miR-214 derived from lung adenocarcinoma may disrupt bone homeostasis by enhancing bone resorption. Exosomal miR-214 can be released by lung adenocarcinoma cells, enters peripheral circulation, and is taken up by osteoclasts, consequently stimulating osteoclast differentiation. The enhanced bone resorption alters the bone microenvironment by releasing multiple cytokines and growth factors favoring cancer cells. The circulating cancer cells migrate to bone, proliferate, and colonize, resulting in the formation of metastasis. Furthermore, osteoclasts derived exosomal miR-214 may in turn contribute to cancer progression. In this way, the exosomal miR-214 from osteoclasts and lung adenocarcinoma cells mediates the positive interaction between bone resorption and bone metastasis. The levels of exosomal miR-214 in the peripheral circulation may help predict the risk of bone metastasis. The exosomal miR-214 may be a potential therapeutic target for both prevention and treatment of bone metastasis in patients with lung adenocarcinoma.
骨转移与骨微环境的改变密切相关。在本文中，我们假设外泌体可能通过转运miR-214参与“恶性循环”。miR-214在肺腺癌中高表达，且与肺癌进展程度密切相关。作为骨稳态的关键调节因子，miR-214通过外泌体微小RNA的方式促进破骨细胞分化并介导破骨细胞与成骨细胞之间的细胞间通讯。因此，源自肺腺癌的外泌体miR-214很可能通过增强骨吸收来破坏骨稳态。外泌体miR-214可由肺腺癌细胞释放，进入外周循环，并被破骨细胞摄取，从而刺激破骨细胞分化。增强的骨吸收通过释放多种有利于癌细胞的细胞因子和生长因子改变骨微环境。循环中的癌细胞迁移至骨，增殖并定植，导致转移灶形成。此外，破骨细胞衍生的外泌体miR-214可能反过来促进癌症进展。这样，来自破骨细胞和肺腺癌细胞的外泌体miR-214介导了骨吸收与骨转移之间的正向相互作用。外周循环中外泌体miR-214的水平可能有助于预测骨转移风险。外泌体miR-214可能是预防和治疗肺腺癌患者骨转移的潜在治疗靶点。
