骨肉瘤淋巴结转移的研究进展

Research progress of lymph node metastasis in osteosarcoma

骨肉瘤(osteosarcoma,OS)是儿童和青少年最常见的原发性恶性骨肿瘤,具有侵袭性强且易发生转移的特点,恶性程度高。骨肉瘤的转移方式主要包括血行转移(最常见为肺转移)和淋巴结转移,相较肺转移,骨肉瘤淋巴结转移的预后更差。目前临床上经常忽视对初诊骨肉瘤患者进行区域淋巴结筛查,对于治疗骨肉瘤淋巴结转移亦无规范标准的方案。骨肉瘤淋巴结转移的两个核心机制是具有转移能力的骨肉瘤细胞浸润淋巴管和骨肉瘤细胞诱导淋巴管新生,但目前仍无法完整阐明其发生、发展的机制。此外,骨肉瘤细胞到达区域淋巴结自适应增殖后,可能再通过淋巴系统和血液系统紧密的解剖学关系向靶器官肺部进行远处转移,其生物学过程涉及多种细胞因子和信号通路。骨肉瘤细胞直接侵袭病灶周围淋巴管、骨肉瘤细胞通过血管内皮生长因子(vascular endothelial growth factor,VEGF)-C/VEGFR-3信号轴诱导淋巴管新生、骨肉瘤细胞通过Hsp5B和Wnt/β-catenin信号通路改造淋巴结微环境以适应生存、骨肉瘤细胞经上皮-间充质转化促使其从淋巴结转移至肺部,小分子化合物抗骨肉瘤淋巴结转移,本文从以上几个方面进行综述,以期为骨肉瘤淋巴结转移的机制研究和药物研发提供更多信息。

Osteosarcoma(OS)stood as the most prevalent primary malignant bone tumor among children and adolescents,characterized by its aggressive nature and high propensity for metastasis,thus earning its classification as a highly malignant disease.The primary routes of metastasis in osteosarcoma encompassed hematogenous dissemination(the most common metastasis was lung metastasis)and lymph node involvement,with lymph node metastasis carrying a notably poorer prognosis when contrasted with lung metastasis.However,it was noteworthy that,at that time,clinical practice often overlooked the crucial aspect of conducting regional lymph node screening for newly diagnosed osteosarcoma patients,and there remained a dearth of standardized treatment protocols for osteosarcoma lymph node metastasis.The intricate mechanisms at the heart of osteosarcoma lymph node metastasis primarily revolved around the infiltration of lymphatic vessels by osteosarcoma cells possessing metastatic capabilities and the induction of lymphatic vessel formation by these cells.Nevertheless,it was imperative to underscore that our understanding of the comprehensive mechanisms underpinning the initiation and progression of these processes still remained incomplete.Moreover,following the adaptive proliferation of osteosarcoma cells within regional lymph nodes,there existed a complex biological process that involved a myriad of cytokines and signaling pathways.This process facilitated the metastasis of osteosarcoma cells to distant target organs,most notably the lungs,by virtue of the intimate anatomical relationships between the lymphatic and circulatory systems.Consequently,that comprehensive review sought to provide an all-encompassing exposition on various facets of osteosarcoma lymph node metastasis.These facets included the direct invasion of surrounding lymphatic vessels by osteosarcoma cells,the osteosarcoma cell-induced development of lymphatic vessels through the VEGFC/VEGFR-3 signaling axis,the remodeling of the lymph node microenvironment by osteosarcoma cells via Hsp5B and the Wnt/β-Catenin signaling pathway to ensure their adaptation and survival,the epithelial-mesenchymal transition of osteosarcoma cells promoting metastasis from lymph nodes to the lung,and the utilization of small-molecule compounds in the battle against osteosarcoma lymph node metastasis.The aim was to provide a comprehensive and systematic elucidation of the intricate mechanisms governing osteosarcoma lymph node metastasis and to furnish invaluable insights for the development of therapeutic strategies.