Tissue Geometry
Plays Crucial Role in Breast Cell Invasion
Behind the Cancer Headlines®
Researchers with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have created a first-of-its-kind model for studying how breast tissue is shaped and structured during development. The model may shed new light on how the misbehavior of only a few cells can facilitate metastatic invasion. It shows that the development of breast tissue, normal or abnormal, is controlled not only by genetics but also by geometry. Though created specifically for the study of breast tissue, this model should also be applicable to the study of tissue development in other organs as well.
In a paper published in the journal Science, Bissell et. al. describe a study in which the branching of mouse epithelial tubules (hollow tubes made from epithelial cells that form the network of milk ducts in the mature female breast) in culture were subjected to control through a three-dimensional micropatterned assay. Using a special algorithm to quantify the extent of branching, the researchers found that the geometric shape of the tubules determines where branching takes place. This may potentially affect where and how a malignancy spreads.
“Our results reveal that tissue geometry can control the morphogenesis of breasts and other organs by defining the local cellular branching microenvironment,” said Bissell, a Distinguished Scientist with Berkeley Lab’s Life Sciences Division, who was the principal investigator for this study. “This finding is important not only for understanding how tissue and organs get their organized shapes and patterns, but may in the future reveal mechanisms to control cancer invasion and metastasis.”
The process of normal branching morphogenesis is precise and quantitative, but invasionary; when something goes wrong the process may lend itself to metastasis. With this demonstration of how the normal function of branching morphogenesis is controlled, Bissell believes researchers can now look for ways in which faulty tubule geometry leads to malignancy.
“In breast cancer, it is most often metastasis rather than the primary tumor that kills a patient,” said Bissell. “We have learned something really dramatic about the regulation of normal branching morphogenesis and this should help us understand how and why things go wrong. Our next step is to put pre-malignant cells – cells that are already losing their way but are not yet malignant – into our model and see what happens. When we do, perhaps this will provide us with new ideas for intervening and preventing pre-malignant cells from becoming fully malignant.”
SOURCES:
Science,
U.S. Department of Energy’s Lawrence Berkeley National Laboratory (http://www.lbl.gov)