ABSTRACT
Undoubtedly, normal and cancerous phenotypes of the mammary gland have been among the precursor models to establish 3D cell culture methods. This is likely due to the enormous impact of breast cancer in the world as well as a strong will to decrease the burden that this disease has bestowed on many populations. In the breast cancer field it has been recognized early on that cancer cannot be understood unless we also decipher the homeostasis of the normal tissue (Bissell 1981). Moreover, to this date preventing tumors from developing is one of the highest challenges in cancer research; as such, “primary prevention” is the only way
15.1 Introduction .................................................................................................. 315 15.2 On-a-Chip Models of the Normal Breast and of Mammary Tumors ........... 319
15.2.1 The Normal Breast Epithelium ......................................................... 320 15.2.2 Ductal Carcinoma In Situ ................................................................. 321 15.2.3 Invasive Ductal Carcinoma .............................................................. 321 15.2.4 Breast Cancer Metastasis .................................................................. 323
15.3 Improved Models for Drug Discovery and Screening .................................. 325 15.3.1 Models Used for Drug Screening in Breast Cancer ......................... 326 15.3.2 Integration of Biosensors within on-a-Chip Models ........................ 328 15.3.3 High-Throughput Screening with Organs-on-Chips ........................ 330
15.4 Perspectives for Precision Medicine ............................................................. 331 15.5 Concluding Remarks .................................................................................... 334 Acknowledgments .................................................................................................. 335 References .............................................................................................................. 335
to reduce a globally rising incidence of breast cancer (Lelièvre and Weaver 2013). Therefore, recapitulating normal phenotypes and notably, the polarity axis, a fundamental feature of epithelia, was emphasized early on (Barcellos-Hoff et al. 1989; Plachot and Lelièvre 2004). The mammary gland is made of a monolayer of luminal epithelial cells delineated by a layer of myoepithelial cells lined against a specialized type of extracellular matrix (ECM), the basement membrane. This epithelium is arranged into ducts of decreasing diameter as they branch out to ultimately lead to terminal ductal glandular units containing multiple acini where the milk is secreted (Figure 15.1a). Milk flows through the ductal tree to reach the opening to the external environment at the nipple. The most frequent breast disease is cancer with tumors that usually grow within the lumen of the duct before cutting through the basement membrane and expanding inside the stroma as cells become invasive (Hodges et al. 2014). Lymph vessels and blood vessels are plentiful within the breast parenchyma and provide two modes of dissemination of breast cancer cells to colonize other tissues and organs.
