Investigating the role of cardiac extracellular matrix in inhibition of cancer progression

Some organs, such as the lung, breast, and prostate, are highly susceptible to cancer. In contrast, the heart is rarely affected by both primary and secondary cancers. Previous data obtained in my hosting laboratory indicate that cancer cells ectopically injected into the heart grow poorly. The extracellular matrix (ECM) is an intricate network of both structural and functional macromolecules that are central to the structural integrity of tissues and behavioral regulation of cells. It is well established that the biology and clinical behavior of cancer may be modulated by its interaction with the tumor microenvironment, regulating cancer cell survival, proliferation, and invasive properties. A plausible and intriguing possibility is that ECM in the adult heart contributes to inhibiting cancer formation and progression. <br><br> To experimentally explore this possibility, we compared the composition and mechanical properties of cardiac ECM with those of lung ECM, as the lung is often colonized by cancer cells. We used two complementary approaches to obtain and study organotypic ECM: first, we decellularized the ECM from the two organs and, second, we purified both cardiac and lung primary fibroblasts (FBs) and let them produce ECM ex vivo. In both cases, the obtained ECM was characterized by JPK II atomic force microscopy (AFM), proteomics, and live cell time-lapse imaging, to assess the capacity of the organotypic ECMs to support the migration of cancer cells. <br><br> Our study provides new insights into the contribution of the adult cardiac ECM to the anti-tumorigenic environment. The specific cardiac ECM components may be used as innovative biotherapeutics to inhibit the migratory capacity of cancer cells in aggressive cancers.