Sialome Dynamics in Mammary Gland Physiology and Cancer

Breast tissue changes dramatically throughout a womans life, such as during the menstrual cycle, pregnancy, breastfeeding, and beyond. The breast tissue also changes on a microscopic level, especially in the way certain sugar molecules called sialic acids are added to proteins and lipids. This process, known as sialylation, plays a key role in how cells organize themselves, how they communicate with the immune system, and how they interact with microorganisms. In healthy tissue, this process is tightly regulated, but in diseases like breast cancer, it can be hijacked. In this project, we aim to uncover how this sugar-based language functions in healthy breast tissue and milk, and how it is altered in breast cancer. Our previous work has shown that the mammary gland has a surprisingly complex sialylation system, that milk contains unique sialic-acid-rich molecules, and that breast cancer uses sialylation as a way to avoid destruction by the immune system. We believe that the dynamic phases of the mammary gland, including the menstrual cycle, pregnancy, lactation, and involution, produce a wide range of specific sialic acid patterns. We hypothesize that these patterns play an important role in supporting infant health through milk. At the same time, we suspect that some of these natural patterns are mimicked or distorted in breast cancer. By mapping out the healthy sialylation landscape of the mammary gland, we hope to uncover clues that will help us better understand, diagnose, or even treat breast cancer. To do this, we will use miniature, lab-grown versions of breast tissue, so called mammary organoids, to study how pregnancy signals and inflammatory molecules affect sialylation. We will also investigate how different sialylation pathways shape the sugar landscape of milk. Finally, we will compare sialylation in healthy mammary cells with that in breast cancer cells, to identify specific molecular patterns that could serve as biomarkers or treatment targets. This is the first project to comprehensively map the mammary gland sialylation landscape. By combining our expertise in glycobiology, immunology, and cancer research, and through a close collaboration between Austria and Japan, we aim to uncover fundamental principles of breast biology and disease. Ultimately, by decoding this hidden sugar language, we hope to contribute to better breast cancer diagnostics and improved understanding of how milk supports the developing infant.