Detail of breast epithelial cells in culture undergoing ductal elongation and side-branching. [Haruko Miura, © Helmholtz Zentrum Munich]
Detail of breast epithelial cells in culture undergoing ductal elongation and side-branching. [Haruko Miura, © Helmholtz Zentrum Munich]

By recapitulating the normal development of breast tissue, scientists hope to learn how development can go wrong and culminate in breast cancer. Ultimately, tissue development consists of cellular processes, which in the case of breast tissue, are capable of being shaped by physical conditions in the cellular environment, which may be compliant or rigid.

According to scientists at Helmholtz Zentrum München, it is now possible to recreate compliant or rigid cellular environments in a new three-dimensional cell culture system. These scientists developed a transparent gel that supports the division and spread of breast cells. The cells can also divide and generate hollow ducts to form a network of branches and terminate in grape-like structures, modeling the regenerative capacity of breast tissue.

The new cell culture system was described June 12 in the journal Development, in an article entitled, “Quantification of regenerative potential in primary human mammary epithelial cells.” The article described how the system allowed researchers to observe how regenerative capacity, necessary to sustain function throughout an adult woman’s reproductive lifespan, but subject to misdirection during cancer, can be influenced by physical properties.

“We were able to demonstrate that increasing rigidity of the gel led to increased spreading of the cells, or, said differently, invasive growth,” explained Jelena Linnemann, first author of the study. “Similar behavior was already observed in breast cancer cells. Our results suggest that invasive growth in response to physical rigidity represents a normal process during mammary gland development that is exploited during tumor progression.”

Co-author Lisa Meixner added that “with our assay, we can elucidate how such processes are controlled at the molecular level, which provides the basis for developing therapeutic strategies to inhibit them in breast cancer.”

Another reason the mini-mammary glands represent a particularly valuable tool is, because the cells that build these structure are directly isolated from patient tissue. In this case, healthy tissue from women undergoing aesthetic breast reduction is used.

“After the operation, this tissue is normally discarded,” noted co-author Haruko Miura. “For us, it is an experimental treasure chest that enables us to tease out individual difference in the behavior of stem and other cells in the human mammary gland.”

“In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis,” the Development article read. “Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland.”

Experimental models that are based on patient-derived tissue constitute a corner stone of basic and applied research. “This technological break-through provides the basis for many research projects, both those aimed to understand how breast cancer cells acquire aggressive traits, as well as to elucidate how adult stem cells function in normal regeneration”, says Christina Scheel, head of the study.