Wang Jingwen, Hu Zhandong, Qian Xuejiao, Xin Weiwei, Cai Wenjuan, Tang Jianwu
Department of Pathology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, People's Republic of China.
Department of Respiratory medicine, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, People's Republic of China.
J Inflamm Res. 2025 Aug 9;18:10741-10750. doi: 10.2147/JIR.S535351. eCollection 2025.
Cancer cell lymphatic endothelialization refers to the transformation of cancer cells into lymphatic endothelial cells through complex cellular and molecular mechanisms, which involve transdifferentiation of cancer cells and their fusion with endothelial cells, both modulated by multiple signaling pathways. This process reflects a dual phenotype comprising features of both cancer cells and lymphatic endothelial cells. The expression of lymphatic-specific markers, including PDPN, LYVE1, PROX1, and SOX18, serves as molecular evidence of this process. Histopathologically, this phenomenon is manifested through lymphangiogenic mimicry, which can be classified into lymphatic-like, mosaic, and lymphatic types. This study presented a theoretical framework to elucidate the developmental mechanisms driving cancer cell lymphatic endothelialization and provided a new theoretical basis for understanding the cellular origin of tumor-associated neolymphatic vasculature and introduces new pathways for investigating mechanisms of tumor lymphangiogenesis and metastasis, thereby providing potential avenues for clinical treatment strategies.
癌细胞淋巴管内皮化是指癌细胞通过复杂的细胞和分子机制转化为淋巴管内皮细胞,这一过程涉及癌细胞的转分化及其与内皮细胞的融合,二者均受多种信号通路调控。该过程反映了一种兼具癌细胞和淋巴管内皮细胞特征的双重表型。包括Podoplanin(PDPN)、淋巴管内皮透明质酸受体1(LYVE1)、prospero同源物1(PROX1)和SRY-盒转录因子18(SOX18)在内的淋巴管特异性标志物的表达是这一过程的分子证据。在组织病理学上,这一现象通过淋巴管生成拟态表现出来,可分为淋巴管样、镶嵌样和淋巴管型。本研究提出了一个理论框架,以阐明驱动癌细胞淋巴管内皮化的发育机制,为理解肿瘤相关新生淋巴管的细胞起源提供了新的理论基础,并为研究肿瘤淋巴管生成和转移机制引入了新途径,从而为临床治疗策略提供了潜在途径。
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