Mechanisms of Cancer Cell Lymphatic Endothelialization in Tumor Lymphangiogenesis and Metastasis: A Comprehensive Review

Abstract

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.

Keywords: cancer cell lymphatic endothelialization; lymphangiogenesis molecules; lymphangiogenic mimicry; tumor lymphangiogenesis; tumor lymphatic metastasis.

Figure 1

Lymphatic endothelialization of cancer cells and tumor lymphangiogenesis and lymphatic metastasis. A. Mimic lymphatic vessel type B. Mosaic lymphatic vessel type C. lymphatic vessel type—represent the initial, intermediate transition, and terminal stages of the endothelialization process, respectively.