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.
Cancer progression is closely related to changes in the structure and mechanical properties of the tumor microenvironment in a complex and not well-understood manner. In many solid tumors, including pancreatic cancer, the complex interplay among the different components of tumor microenvironment leads to a desmoplastic reaction associated with fibroblasts activation and collagen overproduction. Desmoplasia is responsible for tumor stiffening, and poses a major barrier to the effective delivery of drugs and has been associated with poor prognosis. Thus, the understanding of the involved mechanisms and the identification of collagen-based signatures that characterize the state of a particular tumor can lead to the development of novel diagnostic and prognostic biomarkers. In this study, pancreatic tumor models were developed employing the human pancreatic cancer cell lines BxPc-3 and MIAPaCa-2 and tissue biopsies were obtained at different stages of cancer progression. Polarized microscopy on picrosirius red stained tumor sections was used in order to assess collagen-based optical signatures in correlation with tumor progression, while Atomic Force Microscopy (AFM) was applied for the nano-mechanical characterization of the samples. The results demonstrated that pancreatic cancer presents unique collagen-based characteristics that can be used as a novel biomarker for cancer diagnosis and prognosis.
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