ReviewTumor-induced lymphangiogenesis: A target for cancer therapy?
Section snippets
Introduction to the lymphatic system and its molecular biology
Lymphatic capillaries are blind-ended vessels which drain lymphatic fluid from peripheral tissues into larger collecting ducts which empty into the venous system, in the main via the thoracic duct. The lymphatic system plays a vital role in maintaining homeostasis, returning to the circulatory system around 10% of the volume of interstitial fluid escaping from tissue capillary beds (the physiology of the lymphatic system is thoroughly reviewed in Guyton and Hall, 1996). Equally importantly, it
The lymphatics and cancer metastasis
The majority of cancer patients die as a result of metastatic dissemination of their tumor, and a key turning point in the course of cancer progression is thus the development of metastatic potential. In this regard, metastasis to regional lymph nodes is often the first indication that a tumor has progressed to metastatic competence, and regional lymph node status is highly clinically significant for the prognostic evaluation of a broad spectrum of tumor types (reviewed in Sleeman, 2000). These
Tumor-induced lymphangiogenesis: a possible therapeutic target for suppressing metastasis
Our current understanding of the importance of tumor-induced lymphangiogenesis for the formation of lymph node metastases suggests that by blocking the activity of key molecules such as VEGFR-3 it should be possible to suppress the onset of metastasis. Although it is unlikely that the growth of pre-existing metastases would be affected, the inhibition of tumor-induced lymphangiogenesis should reduce the onset of new metastases following diagnosis of cancer and its subsequent therapy.
Conclusions
The rapid rise in research into the regulation of lymphangiogenesis in recent years has dramatically increased our understanding of the role the lymphatic vasculature in a number of physiological and pathological processes, including tumor metastasis. We now have the clear prospect of being able to apply this knowledge translationally to the suppression of the onset of the deadliest aspect of cancer, namely metastasis. Despite this promise, considerable work still needs to be done in order to
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