Integrated extracellular matrix signaling in mammary gland development and breast cancer progression
Jieqing Zhu1, Gaofeng Xiong1, Christine Trinkle3 and Ren Xu1,2
1Markey Cancer Center, 2Department of Molecular and Biomedical Pharmacology and 3Mechanical Engineering, University of Kentucky, Lexington, USA
Offprint requests to: Dr. Ren Xu, Ph.D., Department of Molecular and Biomedical Pharmacology, University of Kentucky, BBSRB 741 S. Limestone, Lexinton, KY 40536, USA. e-mail: ren.xu2010@uky.edu
Summary. Extracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain receptors, and dystroglycan, elicits biochemical and biomechanical signals that control cellular architecture and gene expression. These ECM signals cooperate with growth factors and hormones to regulate cell migration, differentiation, and transformation. ECM signaling is tightly regulated during normal mammary gland development. Deposition and alignment of fibrillar collagens direct migration and invasion of mammary epithelial cells during branching morphogenesis. Basement membrane proteins are required for polarized acinar morphogenesis and milk protein expression. Deregulation of ECM proteins in the long run is sufficient to promote breast cancer development and progression. Recent studies demonstrate that the integrated biophysical and biochemical signals from ECM and soluble factors are crucial for normal mammary gland development as well as breast cancer progression. Histol Histopathol 29, 1083-1092 (2014)
Key words: Extracellular matrix, Mammary gland development, Breast cancer progression, Mechano-transduction
DOI: 10.14670/HH-29.1083