The senescence-associated secretory phenotype (SASP) from mesenchymal stromal cells impairs growth of immortalized prostate cells but has no effect on metastatic prostatic cancer cells.
Nicola Alessio, Domenico Aprile, Tiziana Squillaro, Giovanni Di Bernardo, Mauro Finicelli,
Mariarosa AB Melone, Gianfranco Peluso and Umberto Galderisi
Senescent cells secrete inflammatory cytokines, proteases, and other factors, which are indicated as
senescence-associated secretory phenotype (SASP). There are contrasting studies on the role of the SASP in
cancer. Studies suggested that cancer cells may misuse the senescent secretome for their growth. Other
investigations evidenced that the SASP may induce cancer growth arrest, senescence, or apoptosis. These
conflicting data can be reconciled considering that cancer cells can coax senescent cells to secrete factors for
their survival, thus abrogating the SASP's anti-cancer effect. Cancer stage may also have an impact on the
capacity of the SASP to block tumor proliferation and promote senescence. Indeed, senescence is associated
with a permanent cell cycle arrest, which needs functional cell cycle checkpoints. We evaluated the SASP effect
on the in vitro biological properties of PNT2 and PC3 cells, which are immortalized prostate cells and metastatic
prostatic cancer cells, respectively. We evidenced that SASPs, coming either from mesenchymal stromal cells
treated with H202 or with low X-ray doses, induced senescence of immortalized cells but not of cancer cells.
Hence, the SASP released by acute senescent cells should be considered as an effective weapon against pretumorigenesis events rather than an anti-cancer mechanism acting on malignant cells.