Mammary Stroma in Development and Carcinogenesis
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Mammary Stroma in Development and Carcinogenesis Teruyo Sakakura & Yuka Suzuki & Robert Shiurba
Received: 16 January 2013 / Accepted: 10 April 2013 / Published online: 21 April 2013 # Springer Science+Business Media New York 2013
Abstract Mammary glands of adult human females are secretory organs comprised of interdependent epithelial and mesenchymal cells. These cells constitute an assemblage of collecting ducts that end in terminal duct lobular units with hollow alveolar ductules that can differentiate to produce and expel milk. Systemic and maternal hormones, autocrine and paracrine growth factors, and cytokines regulate virtually all phases of mammary gland development. During organogenesis, epithelial and mesenchymal cells interact to form precursors of the parenchyma and stroma in the mature gland. Organogenesis precedes five stages of postnatal development: puberty, pregnancy, lactation, involution, and menopause. Each stage requires a specific set of morphogenetic changes in glandular structure and function. Cycles of cell proliferation, differentiation, and involution may recur until menopause. In addition, physiological responses such as inflammation and pathological events such as tumorigenesis are remarkable for their similarities to embryonic morphogenesis. Here we take a succinct look at the ever-improving understanding of stroma–epithelial interactions and mesenchyme function in mammary gland biology. Keywords Mammary gland . Stroma . Development . Carcinogenesis
T. Sakakura Mie University, Tsu-shi, Mie-ken, Japan e-mail: [email protected] Y. Suzuki Graduate School of Regional Innovation Studies, Mie University, Tsu-shi, Mie-ken, Japan e-mail: [email protected] R. Shiurba (*) Integrative Bioscience and Biomedical Engineering, Waseda University, Tokyo, Japan e-mail: [email protected]
Abbreviations BMP4 Bone morphogenetic protein 4 DMM Dense mammary mesenchyme E Embryonic day FGF10 Fibroblast growth factor 10 protein Fgf10 Fibroblast growth factor 10 gene FP Fat pad precursor Gli3 Glioma-associated zinc finger 3 transcription factor ME Mammary epithelium Nu/Nu Immunodeficient athymic Foxn1nu mouse PTHrP Parathyroid hormone-related peptide SCID Severe combined immunodeficiency
Introduction Growth, development, and neoplastic transformation of the mammary gland require inductive interactions between epithelium and mesenchyme mediated by diffusible bioactive molecules and corresponding cell receptors. This presentday idea was more than 50 years in the making. The mammary gland is an apocrine, milk-secreting gland with a compound tubuloalveolar architecture made up of cells from the ectoderm and mesoderm of the early embryo. It evolved from an invagination of epidermis into an organ found only in animals of the Class Mammalia and is essential for the nourishment of their young. In 1924, developmental biologists Hans Spemann and Hilde Mangold published a seminal paper that demonstrated the concept of embryonic induction definitively [1]. They performed microsurgical transplantation of the dorsal grey c
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