Purinergic mechanisms in breast cancer support intravasation, extravasation and angiogenesis

Several advances have recently expanded models of tumor growth and promoted the concept of tumor homeostasis, the hypothesis that primary tumors exert an anti-proliferative effect on both themselves and subclinical secondary metastases. Recent trials indicate that the characterization of tumor growth as uncontrolled is inconsistent with animal models, clinical models, and epidemiological models. There is a growing body of evidence which lends support to an updated concept of tumor growth: tumor homeostasis. In the case of breast cancer, if not all metastasizing tumors, these advances suggest an inconvenient truth. That is, if breast tumor cells metastasize to distant sites early in the tumorigenesis process, then removal of a breast tumor may hasten the development of its metastases. We explore the heretofore unappreciated notion that nucleotides generated by tumor cells following the secretion of an ADP-kinase can promote metastasis and support angiogenesis. Evidence is presented that blockade of the actions of nucleotides in the setting of newly diagnosed breast cancer may provide a useful adjunct to current anti-angiogenesis treatment.