头颈鳞状细胞癌 (HNSCC) 的骨侵袭显着影响肿瘤分期、治疗选择、预后和生活质量。虽然已知 HNSCC 会引起溶骨性骨侵袭，但我们发现特定的 HNSCC 亚型可以在肿瘤骨界面诱导成骨性骨破坏。这种破坏模式与患者存活率降低和颈部淋巴结转移增加显着相关。进一步的体内和体外实验表明，HNSCC细胞引发成骨细胞异常表型变化，重塑肿瘤骨微环境，促进肿瘤淋巴转移。通过转录组分析，我们发现了与较差预后相关的三个基因：骨桥蛋白 (SPP1)、趋化因子（C-X-C 基序）配体 1 (CXCL1) 和基质金属蛋白 (MMP)9 (MMP9)。我们发现肿瘤-骨界面处的成骨细胞具有异常表型，表现出高 SPP1、MMP9 和 CXCL1 表达。基于这些特征，我们将这种成骨细胞亚群鉴定为“癌症相关成骨细胞（CAO）”。 HNSCC 细胞激活成骨细胞中的 TNF-α/NF-κB 信号通路，将其转化为“CAO”。这些 CAO 显着促进了肿瘤诱导的骨侵袭的进展，促进了癌症的生长和转移。我们首先提供了临床数据和体内外证据，表明 HNSCC 细胞可以通过将成骨细胞操纵为骨侵袭中的“CAO”来促进肿瘤进展。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Bone invasion by head and neck squamous cell carcinoma (HNSCC) significantly impacts tumor staging, treatment choice, prognosis, and quality of life. While HNSCC is known to cause osteolytic bone invasion, we found that specific HNSCC subtypes can induce osteogenic bone destruction at the tumor-bone interface. This destruction mode significantly correlated with reduced patient survival rates and increased neck lymph node metastasis. Further in vivo and in vitro experiments indicated that HNSCC cells triggered abnormal phenotypic changes in osteoblasts to remodel the tumor-bone microenvironment, facilitating tumor lymphatic metastasis. Through transcriptome analysis, we identified three genes-osteopontin (SPP1), chemokine (C-X-C motif) ligand 1 (CXCL1), and matrix metalloprotein (MMP)9 (MMP9) linked to a poorer prognosis. We discovered osteoblasts with abnormal phenotypes at the tumor-bone interface exhibiting high SPP1, MMP9, and CXCL1 expressions. Based on these characteristics, we identified this osteoblast subpopulation as "cancer-associated osteoblasts (CAOs)." HNSCC cells activated the TNF-α/NF-κB signaling pathway in osteoblasts, transforming them into "CAOs." These CAOs significantly contributed to the progression of tumor-induced bone invasion, facilitating cancer growth and metastasis. We first provided clinical data and in vivo and in vitro evidence that HNSCC cells can promote tumor progression by manipulating osteoblasts into "CAOs" in the bone invasion.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.