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Disorders of Growth and Differentiation
Published in Jeremy R. Jass, Understanding Pathology, 2020
Hyperplasia refers to an increase in the number of cells in an organ or tissue. It occurs in response to hormonal stimulation, increased functional demand, an abnormal trophic influence or chronic injury. The enlargement of the female breast at puberty is a good example of physiological hyperplasia mediated by oestrogen acting upon the duct epithelium. During pregnancy there is further hyperplasia mediated by progesterone acting on the lobuloalveolar epithelium.
Reproductive System and Mammary Gland
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Justin D. Vidal, Charles E. Wood, Karyn Colman, Katharine M. Whitney, Dianne M. Creasy
At the distal extent of the duct system in the rodent, the terminal ductules and their associated alveolar buds comprise the lobuloalveolar unit (LAU), which forms the secretory lobule during lactation (Cardiff and Wellings 1999). The analogous structure in the primate is called the terminal ductal lobular unit (TDLU), and both the LAU and TDLU are the major sites responsive to hormonal stimulation (Cardiff and Wellings 1999). The epithelium of the mammary gland is supported by a connective tissue stroma consisting of varying proportions of adipose tissue and collagen, blood vessels, nerve fibers, and cells of the immune system. In the rodent, the stroma consists mainly of adipose tissue with relatively scant collagen generally forming a thin layer investing ducts and alveoli. In comparison, collagen forms a much greater proportion of the mammary gland in dogs and NHPs. In addition to its structural role, the stroma is recognized as being integral to normal mammary development, growth, and function through numerous paracrine interactions with the epithelium (Hovey and Aimo 2010; Hovey et al. 1999; Imagawa et al. 2002; Parmar and Cunha 2004).
Breast Cancer
Published in Dongyou Liu, Tumors and Cancers, 2017
The epithelium of the mammary gland comprises luminal and basal or myoepithelial cells. Lining the ductal lumen, luminal cells secrete milk upon terminal differentiation into lobuloalveolar cells. Located just below the luminal cells, basal or myoepithelial cells ensure ductal contractility to release milk. In addition, breast ducts are infiltrated with stem cells that are tightly regulated to produce all cellular elements for breast ducts and contribute to normal gland development and cycling.
Cross talk of vascular endothelial growth factor and neurotrophins in mammary gland development
Published in Growth Factors, 2020
Kamini Dangat, Amrita Khaire, Sadhana Joshi
Breast milk is the only source of nutrients and bioactive components for the infant during the early postnatal period (Gila-Diaz et al. 2019; Maru et al. 2013). Breast milk composition plays an important role in determining the baby's growth, development and cognition. The mammary gland is one of the few organs that undergoes cycles of growth, differentiation, functional activity, and involution during the postnatal life (Pepper et al. 2000). Mammary glands undergo major changes during lactation to prepare for milk production (Andres and Djonov 2010; Bao et al. 2016). During this period, mammary epithelial cells multiply to produce the lobuloalveolar structures (Islam et al. 2010). The lobuloalveolar growth and differentiation is mediated by angiogenesis to increase blood supply to the mammary gland. This further leads to expansion of the alveoli which are composed of basket-like endothelial “honey combs”. During the second half of pregnancy, alveolar morphogenesis occurs, which is then followed by the structural and functional differentiation of alveolar epithelial cells. These changes are essential for milk fat and protein secretion during the period of lactation (Pepper et al. 2000). Angiogenesis is essential for alveolar development and function, particularly for milk production (Matsumoto et al. 1992; Pepper et al. 2000; Djonov et al. 2001). During pregnancy, the mammary epithelium along with its vasculature undergoes significant growth and proliferation for increased milk production; however the mechanisms coordinating this vascular development are unclear (VanKlompenberg et al. 2016).
Adipokines as therapeutic targets in breast cancer treatment
Published in Expert Opinion on Therapeutic Targets, 2018
The adipose tissue is considered an endocrine organ since it secretes hundreds of cytokines, which are called adipokines. Adipokines are secreted by subcutaneous, visceral, and mammary fat. In regard to breast cancer, adipokines act through endocrine or paracrine modes, when they are secreted by nonmammary and mammary adipose tissue, respectively; additionally, they can act via autocrine mode, when they are secreted by tumor cells. Anatomically, the breast tissue is composed of branched ducts and lobuloalveolar units embedded in connective tissue called mammary adipose tissue. The mammary adipose tissue, mostly composed of adipocytes, constitutes the breast stroma and secretes adipokines. In normal breast, the basement membrane is a barrier between breast ductal cells and mammary adipocytes. Notably, the basement membrane is lost in invasive breast cancer, allowing tumor cells to infiltrate the mammary adipose tissue: this leads to easier paracrine interaction between adipocytes and tumor cells through adipokines. To understand the role of adipokines in breast cancer, it is necessary to fully comprehend the structure and function of mammary adipocytes. The continuous interaction between epithelial cells and adipocytes is characteristic of both normal breast tissue and breast cancer. In breast cancer, the interaction between tumor cells and adipocytes occurs during tumor initiation, progression, invasion, and metastasis. Adipocytes were originally considered as an energy storage. However, it is now clear that they secrete many cytokines and function as an endocrine organ, involved in several cellular processes. Cancer-associated adipocytes (CAAs) play a role in breast cancer progression and are mostly located in the invasive front of breast cancer [2]. CAAs are characterized by small size due to lipolysis, modification of lipid droplets, and remodeling of adipocyte-related basement membrane and extracellular matrix [2].