Advanced in Vitro Models to Study the Cross-Talk beetween Metastases and Bone Microenvironment: which Role for Osteoporosis?

The skeleton is the organ most frequently affected by metastases, whose complications impair dramatically patients quality of life, with a significant impact on health care costs. Although the understanding of the mechanisms underlying the tropism of some tumors to the bone and the development of "vicious circle" of metastases is not yet complete, it is now increasingly evident that the peculiar characteristics of bone microenvironment provide signals that confer a benefit in terms of growth to cancer cells and probably resistance to certain treatments. Aim of the project was to assess the influence that an impaired state of bone remodeling, as during osteoporosis, exerts on the establishment of metastases. To this end an advanced tridimensional in vitro model of bone metastases was developed co- culturing bone from healthy and osteoporotic rats with ret breast cancer cells, after evaluating the feasibility of different kinds of bone segment cultures and characterizing the cell line used. The results showed that the presence of osteoporotic bone influences cancer cells, which develop stronger characteristics of aggressiveness and invasiveness in comparison to cells cultured with healthy bone. The contemporary findings, via a co-culture in vitro model, that tumor microenvironment enhances osteoporotic osteoclasts activity, highlight the complex and mutual influence of tumor cells with bone cells, supporting the hypothesis that the presence of a condition of altered bone metabolism, such as osteoporosis, promotes the development of metastases, which in turn, stimulating OCs to enhance their osteolytic activity, further impoverish an already altered bone, fueling an endless loop.