Discoidin Domain Receptors in Normal Mammary Development and Breast Cancer Progression

Abstract

The interaction of breast epithelial cells with the surrounding extracellular matrix (ECM) is known to play a pivotal role during normal mammary gland development and function. It is also critical during the pathological changes that lead to breast cancer initiation and progression. A bidirectional crosstalk emerges upon interactions of epithelial cells with the ECM, which eventually dictates the genotypic and phenotypic programs that define normal gland function. Consequently, disruption of this communication contributes to the development of malignant phenotypes, which illustrate the process of breast cancer progression. The Discoidin Domain Receptors (DDRs) are collagen-binding receptor tyrosine kinases that are emerging as key mediators of cell−collagen interactions in breast tissues. DDRs signal in response to both basement membrane and interstitial collagens and thus they are well positioned to activate matrix-induced cellular programs during normal mammary gland development and function, and during dissemination of breast cancer cells. This chapter summarizes the current knowledge on the expression and function of DDRs in breast epithelial cells and their potential involvement in physiological and malignant processes. We also discuss the current challenges in understanding DDR expression and function in breast cancer tissues and experimental models and their potential as therapeutic targets.