Engineered Microenvironments to Study Mechanisms of Tissue Tropism in Metastasis

Breast cancer is the second leading cause of cancer death. With 90% of breast cancer deaths associated with metastasis of the original cancer to other organs, metastasis is a vital area of research. Breast cancer preferentially metastasizes to a subset of organs, including the brain, bone, and lung. Different clinical subtypes of breast cancer have different metastatic profiles to these very diverse organs; however, there is no biophysical explanation for metastatic site preference. Through the use of engineered metastatic microenvironments (EMMs), we are investigating how the physiochemical properties of these tissues influence metastatic site preference. Our EMMs consist of cover slips, which present the characteristic adhesive matrix proteins of brain, bone, and lung. Utilizing these EMMs, we have observed that the EMM protein specificity regulates cell area, shape, adhesion, migration speed, and persistence in MDA-MB-231 and BT-549 cell lines. Both cell lines have the same metastatic profile (39% frequency of bone metastasis and 25% frequency of brain metastasis), and show similar results on EMM mimicking bone and brain tissue. As expected from in vivo clinical data, MDA-MB-231 cells are larger, less spherical, adhere faster, migrate faster, and persist in one direction longer on bone mimics than on brain mimics. BT-549 cells show similar patterns, but differ in cell area and persistence. However, these differences are not significant, and the former may be due to a specific blebbing form of migration observed. We are currently engineering a lung EMM, and examining the role of tissue stiffness via PEG-PC hydrogels in dictating tissue tropism in metastasis.