Cancer progression is known to be accompanied by changes in mechano-cellular phenotype that reflected by changes in both the structure and mechanical properties of the tumor microenvironment (TME). Solid tumors, such as breast tumors and sarcomas, stiffen as they grow in a host healthy tissue. Stiffening is caused by an increase in the structural components of the tumor, mainly collagen fibers, and in cancer and stromal cells content. Tumor stiffening can cause blood vessel inefficiency and hypo-perfusion, and as a result, it poses major physiological barriers to the systemic delivery of drugs. Consequently, there is an urgent need for the development of novel biomarkers, that characterize the mechanical state of a particular tumor so as to support the development of novel therapeutic strategies that target the TME. In this work, polarized microscopy on picrosirius red stained tumor sections and immunofluorescence was used in order to assess collagen-based optical signatures in correlation to tumor progression, while Atomic Force Microscopy (AFM) was applied for the nano-mechanical characterization of the samples. Also, approved anti-fibrotic and chemotherapy drugs, were re-purposed so as to target the tumor matrix and alleviate stiffness The results demonstrated that solid tumors presents unique collagen-based signatures that can be combined with nanomechanical fingerprints so as to develop novel biomarkers for cancer prognosis and treatment monitoring.
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