Mechanobiology of Cancer and Wounds: Innovative Approaches for Prognosis, Prevention and Healing

Background: Wounds and cancer share several similar characteristics. Remarkably, while we aim to inhibit invasive migration of cancer cells, we aspire to accelerate migration of normal cells in wound healing. We thus investigate the changes in cell and tissue mechanics, and cell-cell and cell-microenvironment interactions to establish innovative approaches to identify invasion/migration promoting conditions. Our aim is to identify when cancer cells are likely invasive and should be removed (e.g. excised), and to accelerate closure of gaps following resection of a tumor in the context of wound healing. Here, we focus on identification of non-melanoma invasive skin cancer and fibroblasts as model cells for local repair.

Methods: We evaluate the mechanical invasiveness of tissue-samples of suspected non-melanoma cancers by quantifying the amounts of cells attempting forceful invasion and their attained invasion depths on an impenetrable, physiological-stiffness, synthetic gels.

Results: We demonstrate that the mechanical invasiveness of non-melanoma cancers, evaluated with our innovative 2-hr assay, directly agrees with the clinical histopathology and differentiates between Non-invasive and invasive basal and squamous cell carcinomas (i.e. BCC and SCC). We also reveal patient-specific secondary processes e.g. desmoplasia (neoplasm-associated fibrosis). Concurrently, we show that mechanically modifying the microenvironment of cells, e.g. by stretching the cell-substrate, can accelerate cell migration into a gap, in the context of wound healing.

Conclusions: Mechanobiology affects inverse processes such as cancer and wound healing and can be used to control or identify those process.