Deciphering and targeting the molecular mechanisms that drive the mechanically-induced cancer metastasis to bones.

Mechanical abnormalities of the tumor microenvironment (TME) have gained much attention over the last decades as potent drivers of tumor progression. These abnormalities include compressive forces that generate the so-called solid stress.

Solid stress is suggested to affect the metastatic potential of several tumor types, including breast cancer, however the exact molecular mechanisms involved remain to be explored.

Once cancer cells have left the primary tumor site and entered into the blood stream are also exposed to shear stress exerted by blood flow. Shear stress is considered to be lower during flow, and higher during intravascular arrest.

The arrested cancer cells must develop mechanisms of adhesion to efficiently resist such forces for successful extravasation, however the involved mechanisms are elusive. In particular, the third most common secondary tumor site for breast cancer is bone.

There, cancer cells interact with bone-specific cells, that are also exposed to shear forces due to blood flow in the bone environment.

To this end, the applicant proposes to test the hypothesis that the presence of solid stress in TME, and shear stress in the blood stream are important physical parameters that could trigger cancer cell metastasis.

Therefore, it is highly value to identify the molecular mechanisms involved to target and reverse the metastatic process.

The proposed research combines knowledge in the fields of bone and cancer biology and mechano-pathology, bioengineering and biophysics, and cutting-edge techniques.

A pharmaceutical screening will be also performed in vitro and in vivo to suggest possible therapeutic interventions to prevent breast cancer metastasis.

In the proposed project, the fellow will acquire scientific and complementary skills according to her personalized career development plan, while through advanced training and inter-sectoral mobility she will reach a position of professional maturity in research.