Project Details
Projekt
Bone osteotropism: Influence of confinement and mechanical properties of the seeds in the selection of the soil
Applicant
Dr. Aldo Leal-Egana
Subject Area
Biophysics
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 491716269
One of the most slippery questions in cancer pathologies is why metastatic cells target several organs instead of others. A very interesting example is observed in case of breast or prostate cancers, which are likely metastasizing into bone, instead of other organs, in a phenomenon known as osteotropism.Thus, this project intends to address this question from an interdisciplinary perspective, searching for a link between the biomechanical stress sensed by confined cells within primary tumors, and the ability of these cells to invade, colonize and form secondary tumors onto bone tissues.To this purpose, MCF7 and MDA-MB-231 breast cancer cell lines will be entrapped and cultured in artificial primary tumors having elastic values of 5.0, 25 and 50 kPa (measured as Young’s Moduli), before being characterized at biophysical level by single cell traction force microscopy and cell adhesiveness onto artificial bone-like scaffolds. These experiments will be enriched by sampling cells at different time-points post-cell immobilization, with the purpose to create a mechano-temporal map of cancer biomechanics in vitro.Results obtained at biomechnical level will be then supported by RNA-array studies, enabling us finding a physical-molecular correlation between mechanical stress and expression of markers involved in bone metastasis.In the final step of this project, in vitro assays carried out at biomechanical and genetic level will be validated by in vivo studies. Thus, cell invasion assays and formation of secondary tumors will be assessed in mice models, after pre-conditioning cancer cells to the experimental milieus described above.In vitro and in vivo results acquired with breast cancer cells will be complemented to those obtained with the glioma cell line U87-MG, which has been described to have low metastatic affinity for bone, being used as biological control.According to our knowledge this proposal represents the first clear and systematic attempt to understand the influence of the mechanical properties of the seed in the selection of the soil, unraveling relevant knowledge in the field of mechanics of cell invasion, which can be further used to develop new treatments against malignant diseases.
DFG Programme
Priority Programmes
