Development of angiogenic blood vessels during cancer development is well characterized; however, establishment of lymphangiogenic vessels is enigmatic. Eichten et al. assessed premalignant versus malignant alterations in blood and lymphatic vasculature associated with de novo squamous carcinoma development. They report that vasculature acquires angiogenic and/or lymphangiogenic properties, such as increased vessel diameters and increased endothelial cell proliferation, during premalignant progression. Upon malignant conversion, however, the two vessel systems differ considerably. Whereas angiogenic vasculature remains functional throughout malignant progression, only lymphatic vessels in premalignant tissues, low-grade carcinomas, or at peripheries of higher-grade tumors are functional. In contrast, lymphatic vessels in central regions of higher-grade carcinomas are compressed and nonfunctional. These findings support the notion that therapeutic delivery of anticancer agents could be optimized using premalignant or peripheral vasculature of solid tumors where hemodynamic forces support drug delivery. For details, see the article by Eichten et al. on page 5211 of this issue.

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