Lymphatic endothelial cells, tumor lymphangiogenesis and metastasis : New insights into intratumoral and peritumoral lymphatics

• Published in: Cancer and metastasis reviews Vol. 25; no. 4; pp. 677 - 694
• Main Author: JI, Rui-Cheng
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01-12-2006; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Biomarkers, Tumor; Endothelial Cells - pathology; Humans; Lymphangiogenesis; Lymphatic Metastasis - pathology; Medical sciences; Tumors; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Endothelial cell; Lymphatic system; Lymphatic endothelial cells; Lymphatic; Metastasis; Malignant tumor; VEGF-C/-D/VEGFR-3; Cancerology; Vascular endothelium growth factor; Peritumoral lymphatics; Intratumoral lymphatics; Lymphangiogenesis; Tumor cell; Tumor metastasis
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-006-9026-y

Lymphatic metastasis of tumor cells represents a series of extremely complex and sequential processes that include dissemination and invasion into surrounding stromal tissues from primary tumors, penetration into lymphatic walls and implantation in regional lymph nodes, and extravasation or proliferation in parenchyma of target organs. Recent developments in lymphatic biology and research, especially the application of unique molecular markers specific for lymphatic endothelial cells (LECs), LYVE-1, Prox-1 and podoplanin have provided exciting new insights into the tumor microenvironment and LEC-tumor cell interface. To date, established factors for determining the behavior and prognosis of primary tumors have been emphasized morphologically and physiologically, i.e., lymphatic impairment and vessel density, dysfunction of lymphatic valves, interstitial fluid pressure, as well as a series of lymphangiogenic growth factors including VEGF-C/-D, and other cytokines and chemokines. Increasing knowledge of the tumor biological significance in lymphatics within the tumors (intratumoral lymphatics, ITLs) and at the tumor periphery (peritumoral lymphatics, PTLs) has greatly promoted understanding of tumor access into the lymphatic system by inducing lymphangiogenesis or by co-opting preexisting lymphatics. Therefore, the targeting PTLs and ITLs, which have been proposed as an important route for antimetastatic approach, are deemed worthy of further study in various animal tumor models and human tumors.