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
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
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DOI：
10.18632/aging.102172
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发表时间：
2019-08-15
期刊：
影响因子：
5.2
通讯作者：
Galderisi, Umberto
中科院分区：
文献类型：
--
作者：
Alessio, Nicola;Aprile, Domenico;Galderisi, Umberto
衰老细胞分泌炎性细胞因子、蛋白酶和其他因子，这被称为衰老相关分泌表型（senescence associated secretory phenotype， SASP）。关于SASP在癌症中的作用有不同的研究。研究表明，癌细胞可能滥用衰老的分泌组来生长。其他研究证实SASP可能诱导肿瘤生长停滞、衰老或细胞凋亡。考虑到癌细胞可以诱导衰老细胞分泌维持其生存的因子，从而取消SASP的抗癌作用，这些相互矛盾的数据可以得到调和。癌症分期也可能对SASP阻止肿瘤增殖和促进衰老的能力产生影响。事实上，衰老与永久性细胞周期阻滞有关，这需要功能性细胞周期检查点。我们评估了SASP对永生化前列腺细胞PNT2和转移性前列腺癌细胞PC3细胞体外生物学特性的影响。我们证明，来自间充质基质细胞的sasp，无论是H2O2处理还是低x射线剂量，都能诱导永生细胞衰老，但不会诱导癌细胞衰老。因此，急性衰老细胞释放的SASP应该被认为是对抗肿瘤发生前事件的有效武器，而不是作用于恶性细胞的抗癌机制。
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 H2O2 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.