Cellular senescence, a permanent cell-cycle arrest, is an intrinsic barrier against tumorigenesis. It also limits tissue damage response. However, senescent cells can promote tumorigenesis, inflammation and tissue damage in their microenvironment. Senescent cells accumulate in tissues with age and can promote tissue ageing. The soluble factors and extracellular matrix secreted from the senescent cells were reported to execute these cell non-autonomous phenomena. Here we show a novel mechanism that senescent cells use to affect the neighboring cells - the direct protein transfer. Our results demonstrate that proteins are preferentially transferred from senescent cells to natural killer cells and to cancer cells. The transfer is strictly depended on cell contact and actin polymerization. Moreover, the transferred proteins lead to functional changes in the recipient cells. We propose that Tunneling Nanotubes (TNTs) is a mechanism that accounts for direct protein transfer from senescent cells. Indeed, we detected TNTs structures between senescent cells and the neighboring cells. Thus, our results reveal a novel mode of communication between senescent cells and their microenvironment. Unraveling the mechanism of the protein transfer from senescent cells might lead to better understanding of tumorigenesis and tissue ageing.
