The mechanical anisotropy of adipose tissues regulates ovarian cancer invasion

Abstract

High-grade serous ovarian cancer, the most common and aggressive form of ovarian cancer, generally metastasises to visceral adipose tissues. In these tissues, the extracellular matrix through which ovarian cancer cells adhere and migrate is confined by the presence and preponderance of adipocytes. How cells migrate in this unique environment is not known, yet critical to understanding metastatic progression. To study these processes, we develop biomimetic organo-hydrogels that recreate structural and mechanical properties of human visceral adipose tissues. We show that ovarian cancer cells present invasive tropism towards organo-hydrogels, replicating the behaviour observed in native adipose tissues. This migration is facilitated by the mechanical anisotropy and microstructure of organo-hydrogels and adipose tissues, allowing the formation of cell force-induced migratory tracks, a process regulated by TGF{beta} in an MMP degradation-independent manner. These results highlight the contribution of adipocytes to tissue biophysical features as a key regulatory factor of ovarian cancer cell migration.