Abstract:Ever since it was discovered that endothelial cells line lymphatic vessels, investigators have been working on unraveling the mechanisms that control the growth of this distinctive endothelium and its role in normal physiology and human disease. Recent technological advances have ushered in a new era of "omics" research on the lymphatic system. Research on the genome, transcriptome, proteome, and metabolome of lymphatics has increased our understanding of the biology of the lymphatic vasculature. Here, we intr… Show more
“…Lymph node metastasis is considered to have a major prognostic value, boasting characteristics such as tumor aggression and a worse cancer survival rate. It is now generally accepted that lymphangiogenic factors and lymphangiogenesis promote metastasis to lymph node and distant organs [ 5 ]. Intra- and peritumoral lymphatic vessels are now hypothesized to play an important role in the interaction between lymphatic endothelial cells (LECs) and cancer cells, leading to cancer metastasis.…”
“…Lymph node metastasis is considered to have a major prognostic value, boasting characteristics such as tumor aggression and a worse cancer survival rate. It is now generally accepted that lymphangiogenic factors and lymphangiogenesis promote metastasis to lymph node and distant organs [ 5 ]. Intra- and peritumoral lymphatic vessels are now hypothesized to play an important role in the interaction between lymphatic endothelial cells (LECs) and cancer cells, leading to cancer metastasis.…”
“…The primary physiological role of the lymphatic system is to filter the body waste products and fight infection through innate and specific immunity. For a more detailed review of the anatomy and physiology of the lymphatic system, additional information is available in separate reviews [ 83 – 85 ]. Fig.…”
Section: Summary and Future Perspectivesmentioning
The lymphatic system is a complicated system consisting of the lymphatic vessels and lymph nodes draining the extracellular fluid containing cellular debris, excess water and toxins to the circulatory system. The lymph nodes serve as a filter, thus, when the lymph fluid returns to the heart, it is completely sterile. In addition, the lymphatic system includes the mucosa-associated lymphoid tissue, such as tonsils, adenoids, Peyers patches in the small bowel and even the appendix. Taking advantage of the drainage system of the lymphatics, cancer cells enter the lymphatic vessels and then the lymph nodes. In general, the lymph nodes may serve as a gateway in the majority of cases in early cancer. Occasionally, the cancer cells may enter the blood vessels. This review article emphasizes the structural integrity of the lymphatic system through which cancer cells may spread. Using melanoma and breast cancer sentinel lymph node model systems, the spread of early cancer through the lymphatic system is progressive in a majority of cases. The lymphatic systems of the internal organs are much more complicated and difficult to study. Knowledge from melanoma and breast cancer spread to the sentinel lymph node may establish the basic principles of cancer metastasis. The goal of this review article is to emphasize the complexity of the lymphatic system. To date, the molecular mechanisms of cancer spread from the cancer microenvironment to the sentinel lymph node and distant sites are still poorly understood and their elucidation should take major priority in cancer metastasis research.
“…The lymphatic system provides a major pathway for tumor spread. There is proven correlation between tumoral lymphangiogenesis, invasion of the lymphatic system, and distant/hematogenous metastasis [ 4 , 5 ]. Vascular endothelial growth factors (VEGF)-C and -D have been associated with high metastatic potential to the lymphatic system.…”
Section: Lymphatic Spread Of Cancermentioning
confidence: 99%
“…VEGF-C and -D induce lymphangiogenesis through activation of vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly produced by the lymphatic endothelial cells. Tumors overexpressing VEGF-A, neutropilin-2, VEGF-C, and VEGF-D are associated with increased potential for lymphatic spread [ 4 , 5 , 6 , 7 , 19 ].…”
Section: Lymphatic Spread Of Cancermentioning
confidence: 99%
“…These processes induce increased growth of blood and lymphatic vessels to the tumor and surrounding regions, providing additional nutrients for tumor growth and more pathways for spread. Increased lymphangiogenesis is associated with higher probability of metastasis through the lymphatic system, including lymph nodes [ 4 , 5 , 6 , 7 ]. The most commonly used cancer staging system is the TNM system, where N represents lymph node status.…”
The lymphatic system is an anatomically complex vascular network that is responsible for interstitial fluid homeostasis, transport of large interstitial particles and cells, immunity, and lipid absorption in the gastrointestinal tract. This network of specially adapted vessels and lymphoid tissue provides a major pathway for metastatic spread. Many malignancies produce vascular endothelial factors that induce tumoral and peritumoral lymphangiogenesis, increasing the likelihood for lymphatic spread. Radiologic evaluation for disease staging is the cornerstone of oncologic patient treatment and management. Multiple imaging modalities are available to access both local and distant metastasis. In this manuscript, we review the anatomy, physiology, and imaging of the lymphatic system.
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