Leal-Egaña Group Bone osteotropism: influence of inclusion and mechanical properties of seeds on soil selection

One of the most complex questions in cancer pathology is why tumor cells prefer certain organs to others when metastasizing. An interesting example is observed in the case of breast and prostate cancer, which form metastases preferentially in bones rather than organs. This process is called osteotropism. 

This project addresses the above question from an interdisciplinary perspective by drawing a link between the biomechanical stress experienced by trapped cells in the primary tumor and the ability of these cells to invade bone tissue, colonize, and form secondary tumors. For this purpose, MCF7 and MDA-MB-231 breast cancer cell lines are entrapped and cultured in artificial primary tumors. The elasticity of the artificial primary tumor is 5.0, 25, and 50 kPa (Young's Moduli). The cell lines are then biophysically characterized using single-cell traction force microscopy and cell adhesion on artificial, bone-like scaffolds. The two experiments will then be extended by characterizing cells at different time points after cell immobilization so that a mechanical time-dependent map of cancer biomechanics can be generated in vitro, and the biomechanical results will be supported by RNA sequencing to demonstrate a physical-molecular correlation between mechanical stress and expression of the markers in bone metastases. In the project's final step, the in vitro experiments will be validated by in vivo studies, where experiments on cell invasion and secondary tumor formation will be performed in mice with cells derived from the above-described milieus. In vitro and in vivo results of the breast cancer cell lines are compared with the glioblastoma cell line U87-MG results. The latter has a low affinity for the formation of metastases in bone tissue and therefore serves as a biological control.

To our knowledge, this project proposal is the first clear and systematic attempt to understand the influence of the mechanical properties of seeds in soil. It will uncover relevant knowledge about the mechanics of cell invasion that can be used to develop new treatments for malignant diseases.