Introduction on Angiogenesis in Breast Cancer

Abstract

Angiogenesis is a complex process involving the growth and organization of blood vessels, and has been studied for over 30 years. Many excellent reviews about the distinct events that lead to the production of a vascular and microvascular tree exist already. Of course, much of the work has been focused on the angiogenesis present in pathologic states, notably oncogenesis and inflammatory diseases. Starting with the original work of Paget and then continued by many other researchers spearheaded by the original and groundbreaking work of Judah Folkman, Josh Fidler, and Mina Bissell, studies of abnormal angiogenesis have focused on understanding the complex interactions between the supporting stroma and the “diseased” index cell. In particular, a growing concern about tissue-specific signals has raised awareness that although governed by common principles, the details of abnormal angiogenesis require models that realistically reflect the intricacies of tissue specificity. We believe that this may derive from the fact that the growth of blood vessels in embryonic life develops following dynamic and plastic programs that depend on tissue differentiation. Because you are reading this journal, we surmise you have embraced the overarching hypothesis that tissue specificity must be considered when studying development and pathogenesis in the mammary gland. In this volume, we undertake to provide the readers of Mammary Gland Biology and Neoplasia with a series of articles that deal with novel hypotheses of the angiogenesis process in the breast. We strive to make this volume an excellent resource for researchers entering the field and to provide a starting point to ponder this fascinating process, which holds such great potential as a therapeutic target. Some of this potential is already being realized, as you will see explained in the following chapters. The chapters by Mercurio et al. and Merajver and Usmani identify novel aspects of signaling in angiogenesis in the mammary gland. The Mercurio group has been at the forefront of our understanding of integrin regulation. By now turning their attention to this regulation in mammary carcinogenesis, they clarify the potential for vascular endothelial growth factor to play a major role in breast cancer survival and success at metastatic sites. They further conceive a hypothesis for VEGF to have a role beyond its known effects on endothelial cell survival and angiogenesis per se. This chapter is especially useful for those concerned with the early steps in breast cancer metastasis and derangement of cell adhesion. Complementing this chapter, Merajver and Usmani review the impact of Rho proteins, which to a large extent are signaling upstream of integrins in response to G proteincoupled receptor stimulation. Although the Rho proteins have been traditionally associated with budding and membrane focal adhesions, it is now additionally known that they are required for metastasis in breast cancer; as such, they constitute especially attractive potential targets for therapeutic interventions. The Merajver lab has been studying the most lethal form of breast cancer—inflammatory breast cancer—for over 10 years; this chapter reflects some of the key insights they have gained through that work, and includes cutting edge research into angiogenesis-related targets that is reaching the clinic. J Mammary Gland Biol Neoplasia (2005) 10: 281–282 DOI 10.1007/s10911-006-9000-x