Angiogenesis,lymphangiogenesis, and tumor progression

Angiogenesis plays an important role for the growth and metastasis of malignant tumors. The "angiogenic switch" may even precede the development of other traits that contribute to the malignant phenotype. The switch to the angiogenic phenotype is thought to be induced by a change in the balance of positive and negative regulators of angiogenesis. The main emphasis of this review is to discuss the role of two potent endogenous inhibitors, thrombospondin-(TSP-)1 and TSP-2, for the development and progression of tumors. The recent identification of specific growth factors for lymphatic vessels and of new lymphatic-specific markers provided evidence for an active role of the lymphatic system during the metastasis process. Endogenous inhibitors of lymphangiogenesis have not yet been detected and until recently it was unclear whether or not the known endogenous angiogenesis inhibitors may also have some additional effects on lymphangiogenesis. The data provided indicate that angiogenesis inhibitors specifically inhibit tumor progression but fail to block the conversion of premalignant to malignant tumors. Moreover, angiogenesis inhibitors may have some elective effects on the formation of blood vessels but not on lymphatic vessels. These results will have implications for the further development and clinical use of angiogenesis inhibitors since they indicate that inhibitors might most efficiently be used to target early stages of tumor progression and in combination with specific inhibitors of lymphangiogenesis.