The Importance and Role of the Lymphatic System During Metastasis

The lymphatic system functions as a key microenvironmen-tal adjunct to the vascular system for the spread of metastasizing cells to their secondary sites.123,124 The importance of the lymphatic system as an avenue of metastatic dispersion is underscored by the prognostic value associated with the spread of cancers to regional lymph nodes125,126 and the impact of the removal of such lymph nodes on the prevention of metastasis and overall survival.127,128

That peritumoral lymphatics play an integral role in metastatic spread is established129,130; what is more controversial is the role that intratumoral lymphatics play.131-134 This controversy has been fueled by the recent discovery of lymphatic-specific molecules such as VEGF C,135-137 VEGF D,138,139 and VEGFR-3.140,141 An association between tumor expression of these lymphatic-specific factors and metastasis has been established, suggesting that tumor lym-phangiogenesis is an important prognostic indicator in the same fashion as is tumor angiogenesis.142,143 It is anticipated that the metastatic significance of intratumoral lymphatics and lymphangiogenesis will be more firmly defined as additional lymphatic-specific molecules are identified and the mechanism of tumor-associated lymphangiogenesis is further examined.

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