Figure 4

From: Killers creating new life: caspases drive apoptosis-induced proliferation in tissue repair and disease

Figure 4

AiP in cancer and treatment failure. Emerging clinical studies have found that high levels of activated caspase-3 in tumors is associated with poor prognosis. Possible mechanisms by which caspase-mediated AiP could be contributing to tumorigenesis are modeled here. (a) Tumor repopulation following radiation or chemotherapy: cancer cells sensitive to the cytotoxic treatment initiate apoptosis and some cells trigger an AiP response through the production of PGE2 and other proliferative cytokines. Overall tumor bulk is initially reduced due to the apoptotic death, but the remaining cancer cells—including therapy-resistant cells—are stimulated via AiP to proliferate, repopulating the tumor. Over repeated cycles this could lead to extremely resistant tumors and eventual treatment failure. (b) Growth signals from dying tumor cells stimulate angiogenesis: caspase activation in dying tumor cells has been directly linked to VEGF-A production, a growth factor that promotes angiogenesis and neovascularization of the tumor. (c) Dying vascular endothelial cells also trigger AiP: caspase activation in the VE cells results in PGE2 production, which may stimulate further proliferation of the tumor cells