Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Respiratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Biochem Biophys Res Commun. 2018 Jun 7;500(3):758-764. doi: 10.1016/j.bbrc.2018.04.150. Epub 2018 Apr 24.
While chemotherapy is an important and widely used therapeutic for cancer, it may facilitate cancer metastasis. Herein, we report that human lung cancer cells exert higher invasion and metastasis after chemotherapy. In a human lung cancer xenograft model, chemotherapy promotes the cancer invasion and metastasis in HMGB1-dependent manner. Further studies identify HMGB1-containing nucleosome from chemotherapy-induced apoptotic cancer cells as an effective factor. Such nucleosome functions through TLR4 and TLR9 to drive cancer invasion and metastasis. In lung cancer patients, circulating HMGB1-containing nucleosome is higher in those under chemotherapy, predicting poorly cancer cell differentiation state, enhanced cancer invasion and advanced TNM stages. These findings provide a novel mechanism by which the tumor metastasis is propagated in lung cancer patients, especially in those under chemotherapy, and a clue for developing therapeutic strategies against chemotherapy-induced metastasis.
虽然化疗是一种重要且广泛应用于癌症治疗的方法，但它可能会促进癌症转移。在这里，我们报告说，人类肺癌细胞在化疗后表现出更高的侵袭和转移能力。在人肺癌异种移植模型中，化疗以 HMGB1 依赖的方式促进癌症侵袭和转移。进一步的研究确定了来自化疗诱导的凋亡癌细胞的包含 HMGB1 的核小体是一种有效的因子。这种核小体通过 TLR4 和 TLR9 发挥作用，从而驱动癌症的侵袭和转移。在肺癌患者中，接受化疗的患者循环中含有 HMGB1 的核小体含量更高，这预示着癌细胞分化状态较差、侵袭性增强和 TNM 分期进展。这些发现为肿瘤转移在肺癌患者中传播提供了一个新的机制，特别是在接受化疗的患者中，也为开发针对化疗诱导转移的治疗策略提供了线索。
