Vascular remodelling during the normal and malignant life cycle of the mammary gland

The mammary gland life cycle is exemplified by massive, physiologically dic tated changes in cell number and composition, architecture, and functionali ty. These drastic upheavals, by necessity, also involve the mammary endothe lium, which undergoes angiogenic expansion during pregnancy and lactation f ollowed by ordered regression during involution. In this review, we summari se data obtained using the Mercer methyl methacrylate corrosion cast techni que to analyse the mammary gland vasculature during normal development and carcinogenesis. Concomitant with epithelial cell expansion, the mammary vas culature grows during the first half of pregnancy by sprouting angiogenesis whereas the last half of pregnancy and lactation are characterised by the non-proliferative intussusceptive angiogenesis. The vasculature of the lact ating gland is composed of a well-developed capillary meshwork enveloping t he secretory alveoli with basket-like honeycomb structures. During involuti on, regression of the vasculature is achieved by regional collapse of the h oneycomb structures, capillary retraction, and endothelial attenuation. Thi s process appears partly to involve apoptosis. However, an additional mecha nism involving remodelling without cell death, which we have termed angiome iosis, must exist to explain the morphological observations. Interestingly, in mammary tumours of neuT transgenic mice, both sprouting and intussuscep tive angiogenesis was observed simultaneously in the same nodules, a findin g with potential implications for cancer therapy. The underlying molecular mechanisms controlling angiogenic modulation in the mammary gland, particul arly angiogenic regression and the endothelial:parenchymal interplay, are p oorly understood. However, the data summarised in this review indicate that precisely these molecular mechanisms offer novel alternatives for specific and effective treatment of breast cancer. (C) 2001 Wiley Liss. Inc.