P53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells.

ABSTRACT: The induction of cellular senescence is an important mechanism by which p53 suppresses tumorigenesis. Using a mouse model of liver carcinoma, where cellular senescence is triggered in vivo by inducible p53 expression, we demonstrated that NK cells participate in the elimination of senescent tumors. The elimination of senescent tumor cells is dependent on NKG2D. Interestingly, p53 restoration neither increases ligand expression nor increases the sensitivity to lysis by NK cells. Instead, p53 restoration caused tumor cells to secrete various chemokines with the potential to recruit NK cells. Antibody-mediated neutralization of CCL2, but not CCL3, CCL4 or CCL5, prevented NK cell recruitment to the senescent tumors and reduced their elimination. Our findings suggest that elimination of senesce

SUBMITTER: Iannello A 

PROVIDER: S-EPMC3782044 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature