Three-dimensional culture models of mammary gland

Abstract

The mammary gland is a complex tissue comprised of a branching network of ducts embedded within an adipocyterich stroma. The ductal epithelium is a bi-layer of luminal and myoepithelial cells, the latter being in contact with a basement membrane. During pregnancy, tertiary branching occurs and lobuloalveolar structures, which produce milk during lactation, form in response to hormonal and cytokine signals. Postlactational regression is characterized by extensive cell death and tissue remodeling. These complex developmental events have been difficult to mimic in cell culture although many useful culture models exist. Recently, considerable advances in threedimensional modelling of the mammary gland have been made with the use of collagen and other biomaterials for the study of branching morphogenesis and tumorigenesis, techniques which may enable rapid advances in our understanding of both basic biology and the study of cancer therapeutics.

Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

“…During puberty, the mammary gland undergoes key developmental phases including terminal end bud formation, ductal elongation, and ductal branching that collectively establish a branching network of parenchymal ducts surrounded by a supporting adipose and stroma (48). One explanation for impaired mammary development may be alterations in zinc-dependent functions.…”

Luminal MCF-12A and myoepithelial-like Hs 578Bst cells form bilayered acini similar to human breast

“…Malignant as well as nonmalignant mammary cells have traditionally been studied as monolayer on plastic cell culture dishes, thereby losing their morphological organization and tissue-specific function (Weigelt et al, 2014). Fortunately, progress in tissue engineering and biomaterials have provided researchers with innovative techniques that are now allowing to explore the possibilities of 3D culture, thus bridging the gap between in vitro monolayer cell culture models and expensive in vivo wholeanimal systems (Campbell & Watson, 2009). 3D culture systems promote expression of tissuespecific functions and cellular processes by allowing cells to self-assemble and to receive cues from their neighbouring cells and the surrounding extracellular matrix, which cannot be achieved when cells are plated on plastic cell culture dishes in 2D (Campbell & Watson, 2009;Weigelt & Bissell, 2008).…”

“…Fortunately, progress in tissue engineering and biomaterials have provided researchers with innovative techniques that are now allowing to explore the possibilities of 3D culture, thus bridging the gap between in vitro monolayer cell culture models and expensive in vivo wholeanimal systems (Campbell & Watson, 2009). 3D culture systems promote expression of tissuespecific functions and cellular processes by allowing cells to self-assemble and to receive cues from their neighbouring cells and the surrounding extracellular matrix, which cannot be achieved when cells are plated on plastic cell culture dishes in 2D (Campbell & Watson, 2009;Weigelt & Bissell, 2008). 3D models are particularly useful for the study of protein and gene functions, along with signaling pathways in a physiologically relevant context (Weigelt & Bissell, 2008).…”

“…However, because they are formed using primary cultures, they are hardly genetically manipulable. There is thus still a great need for a simplified, optimized, genetically manipulable, reproducible and physiologically relevant model to recapitulate the normal structure of the functional unit of the human mammary glandthe bilayered acinus (Campbell & Watson, 2009).…”

Novel insights into adiponectin action in breast cancer: Evidence of its mechanistic effects mediated by ERα expression

“…Even though mammary adipose tissue is a component of subcutaneous adipose tissue, which occupies the 56% of the non‐lacting breast tissue and 35% of lactating breast tissue, it exhibits distinctive features from those present in adipose tissue in other body regions. The mammary gland has a complex structure composed of different cell types, including mioepithelial and luminal epithelial cells embedded in a network of adipocytes and fibroblasts, forming a complex stroma termed mammary fat pad . Mammary adipose tissue displays cyclic structure changes upon the cyclical female hormonal pressure in a stable functional interplay with the epithelial cells.…”