Around 70,000 women are diagnosed with breast cancer on an annual basis, in Germany alone. And regardless of the previous breakthroughs in diagnosing and treating the disease, there still exists far more aggressive sub-types of breast cancer that remain a medical mystery and are therefore practically incurable. However, a newly developed model can help bring in a new wave, practices, theories, and ultimately cures to breast cancer; as the experimental model delves into mammary gland biology and standard breast cancer research. In a collaborative effort with their colleagues at the LMU Munich, researchers at the Helmholtz Center in Munich now have the ability to produce a fully realized three-dimensional organoid-structure that resembles regular breast cancer development and function from single patient-derived cells.
The research team, headed by Dr. Christina Scheel, created an assessment wherein sophisticated human breast epithelial cells would be able to reconstruct the three-dimensional biological tissue of the mammary gland. In order to achieve this a transparent gel is utilized that assists in dividing and spreading cells, much like what occurs during the development of the mammary gland during puberty. More specifically, the cells separate and produce hollow ducts that constitute a network of branches that end in grape shaped structures. Following puberty, the mammary gland is constantly redeveloped in order to further provide milk, even after one or more pregnancies. And in spite of their slippery identity, this high cellular activity is in need of cells that have the ability to regenerate, for ex: stem cells. Breast cancer cells can mold stem cells in order to create aggressive traits. To discover how aggressive traits are imparted in breast cancer cells, it is imperative to clarify the operation of normal, healthy, breast stem cells. It is for this reason; Scheel and her team developed the experimental tool.
“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,” said Scheel.
By using their newly developed organoid assessment, the researchers noted that the behavior of regenerative cells is ultimately decided by the physical properties of their environment; as first author of the study, Jelena Linnemann explains:
“We were able to demonstrate that increasing rigidity of the gel led to increased spreading of the cells, or, said differently, invasive growth. 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. 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.”
One other example of why the mini-mammary gland is an extremely invaluable tool is because the cells that are ‘born’ within this structure are separate from patient tissue. In this circumstance, healthy tissue from women undergoing aesthetic breast reduction is used.
“After the operation, this tissue is normally discarded. 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,” said co-author Haruko Miura.
