Cellular senescence, characterized by the irreversible arrest of cellular growth, is important for preventing the development of cancers. However, a number of studies also suggest that alterations in senescent tissues can contribute to tumour malignancies. Now, Michelle R. Dawson and colleagues (Ghosh et al., 2020) investigate the morphological and biophysical changes mesenchymal stem cells (MSCs) undergo during senescence, and whether these influence breast cancer cell behaviour. The authors first establish that senescent MSCs are larger, display altered cytoskeletal and nuclear organization, and are less motile compared to pre-senescent cells. Mass spectrometry analysis confirmed that several proteins involved in cytoskeletal dynamics and nuclear structure were misregulated in senescent MSCs. The authors then develop a 3D matrix interface model, in which co-cultured MSCs and breast cancer cells self-organize into spheroid cultures. They find that senescent cells remodel the surrounding collagen matrix, and that this remodelling promotes invasion of breast cancer cells into collagen. Finally, by inhibiting matrix proteinases and crosslinkers, the authors demonstrate that matrix remodelling is required for breast cancer invasion in the spheroids. Together, this work provides new insights into age-related cancer progression and the role matrix remodelling induced by senescent cells plays therein.
