Abstract
Tumor-associated lymphatic vessels play an important role in tumor progression, mediating lymphatic dissemination of malignant cells to tumor-draining lymph nodes and regulating tumor immunity. An early, necessary step in the lymphatic metastasis cascade is the invasion of lymphatic vessels by tumor cell clusters or single tumor cells. In this review, we discuss our current understanding of the underlying cellular and molecular mechanisms, which include tumor-specific as well as normal, developmental and immunological processes “hijacked” by tumor cells to gain access to the lymphatic system. Furthermore, we summarize the prognostic value of lymphatic invasion, discuss its relationship with local recurrence, lymph node and distant metastasis, and highlight potential therapeutic options and challenges.
Highlights
The lymphatic system is a blind-ended drainage system, composed of initial lymphatic networks present in almost every organ, collecting vessels and lymph nodes (LNs)
We summarize the prognostic value of lymphatic invasion, discuss its relationship with local recurrence, lymph node and distant metastasis, and highlight potential therapeutic options and challenges
Lymph is transported through afferent collecting vessels to draining LNs, percolates through a network of lymphatic sinuses, and leaves the LN via a single efferent collecting vessel that connects to secondary LNs and to the venous circulation via the thoracic duct or the right lymphatic duct (Figure 1A)
Summary
The lymphatic system is a blind-ended drainage system, composed of initial lymphatic networks present in almost every organ, collecting vessels and lymph nodes (LNs). LECs of the outer wall (“ceiling LECs”) of the subcapsular sinus share phenotypic characteristics with LECs of collecting lymphatic vessels and presumably contribute to a tight barrier towards the surrounding tissue, whereas those of the inner lining of the subcapsular sinus (“floor LECs”) and those of cortical and medullary sinuses are more reminiscent of initial LECs and are permissive for transendothelial transport and migration of leukocytes between the lymphatic lumen and the LN parenchyma [7] Due to their function as fluid drainage and molecular and cellular transport system, lymphatic vessels show dynamic phenotypic responses and play important roles in a wide range of pathological conditions, including acute and chronic inflammation as well as cancer [8,9,10]. Efferent lymphatic vessels, various types of sinuses, and corresponding LEC subsets
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