High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4
High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4
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DOI：
10.1016/j.bbrc.2020.07.120
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发表时间：
2020-10-20
影响因子：
3.1
通讯作者：
Sasaki, Akira
中科院分区：
文献类型：
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作者：
Sakamoto, Yumi;Okui, Tatsuo;Sasaki, Akira
侵袭性口腔鳞状细胞癌(OSCC)对上颌骨的破坏给患者的治疗带来了各种问题，导致患者预后和生存率下降。然而，口腔鳞状细胞癌骨质破坏的机制尚不清楚。高迁移率族蛋白1(HMGB1)是一种高度保守的普遍存在的核非组蛋白DNA结合蛋白，已被证明在侵袭性癌症中分泌并调节破骨细胞的形成，在骨破坏过程中发挥重要作用。因此，我们推测口腔鳞状细胞分泌的HMGB1有助于骨破坏。我们的结果表明，HMGB1是由口腔鳞癌的人细胞株产生的，它通过上调成骨细胞和骨细胞中核因子kappaB受体激活物配体的表达来促进破骨细胞的形成，从而促进小鼠破骨细胞性骨破坏。此外，我们发现HMGB1的这些作用是通过晚期糖基化终产物受体和Toll样受体介导的。这些发现表明口腔鳞癌HMGB1及其下游信号通路是治疗晚期口腔鳞癌相关骨破坏的潜在靶点。(C)2020作者。由爱思唯尔公司出版。
Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via upregulation of the expression of receptor activator of nuclear factor kappa-B ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC. (c) 2020 The Authors. Published by Elsevier Inc.