title: Pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis.
abstract: Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system. These axis-related signal molecules could gradually produce waterfall-like cascading effects, mediate differentiation and maturation of LECs, remodel original and neonatal lymphatic vessels, as well as ultimately promote tumor cell chemotaxis, migration, invasion and metastasis to lymphoid tracts. This review summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, the expression changes of these molecules in different anatomic organs or histopathologic types or development stages of various tumors, the characteristics of transduction, implementation, integration of signal networks, the interactive effects on biological behaviors between tumor cells and lymphatic endothelial cells, and their molecular mechanisms and significances in tumor lymphangiogenesis and lymphatic metastasis.
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China.
authors.forename: Salma
authors.initials: S
authors.lastname: Mahoud
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China.
authors.forename: Ahmed Musa Hago
authors.initials: AM
authors.lastname: Bakheet
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Dalian Medical University, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, 9 West, Lvshun Southern Road, Dalian, Liaoning 116044, China. Electronic address: jianwutang@163.com.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Tang
mesh_terms: D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039943:Neuropilin-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D039943:Neuropilin-2; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; C581308:neuropilin-2, human; C581309:FLT4 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Lymphangiogenesis; Pathway-related molecules; Tumor; VEGFC/D-VEGFR3/NRP2 axis; lymphatic metastasis