Table 1. SASP factors.
The SASP is a complex, plastic phenotype that varies with cell type and mode of senescence induction. The SASP factors are categorized according to the fold change in secreted protein level over presenescent controls. The categories are approximate by necessity, as each cell type has different fold changes of each factor. The “senescence inducers” increase the expression of a given factor. “+” indicates well-documented pro-inflammatory proteins; “−” indicates well-documented anti-inflammatory proteins. Factors lacking + or − might also have pro- or anti-inflammatory activity, but these activities are either not well documented or highly context-dependent. Abbreviations: OIS, oncogene-induced senescence; DDIS, DNA-damage-induced senescence; REP, replicative senescence; RAS, oncogenic RAS overexpression; MEK, oncogenic MEK overexpression; XRA, high dose X-irradiation; BLEO, bleomycin treatment; ETOP, etoposide treatment. Cell types: HCA2, BJ – human foreskin fibroblasts; Wi-38, IMR-90 – human embryonic lung fibroblasts; PrECs – normal human prostate epithelial cells; BPH1, RWPE1, PC3 –transformed human prostate epithelial cells; PSC27, PSC31, PSC32 – human prostate fibroblasts. The last names in the reference column refer to the following papers: Acosta: [51]; Bavik: [75]; Coppe: [23] and [76]; Rodier: [56]; Wajapeyee: [52]; Liu: [38]; Krizhanovksy: [44]; Parrinello: [15]; West: [77].
| High increase (4+ fold) | ||||
|---|---|---|---|---|
| Factor | Senescence inducer | Cell type | Reference | |
| GM-CSF | OIS (RAS, MEK), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Acosta, Coppe |
| GROα | OIS (RAS, MEK), DDIS (XRA, BLEO), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3, prostate broblasts (PSC27, PSC31, and PSC32) | Acosta, Coppe, Bavik |
| GROα,β,γ | OIS (RAS, MEK), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Acosta, Rodier, Coppe |
| IGFBP-7 | OIS (BRAF) | + | melanocytes | Wajapeyee |
| IL-1α | OIS (RAS, MEK), DDIS (XRA, BLEO) | + | IMR-90, HCA2, PrECs, BPH1, RWPE1, PC3 | Acosta, Coppe, Liu |
| IL-6 | OIS (RAS, MEK), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Acosta, Rodier, Coppe |
| IL-7 | OIS (RAS), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ | Coppe |
| IL-8 | OIS (RAS, MEK), DDIS (XRA, BLEO), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3, prostate broblasts (PSC27, PSC31, and PSC32) | Acosta, Rodier, Coppe, Bavik |
| MCP-1 | OIS (RAS, MEK), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Acosta, Rodier, Coppe, Liu |
| MCP-2 | OIS (RAS), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ | Coppe |
| MIP-1α | OIS (RAS), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Coppe |
| MMP-1 | OIS (RAS), DDIS (XRA, BLEO), REP | IMR-90, HCA2, WI-38, BJ | Coppe, Liu | |
| MMP-10 | OIS (RAS), DDIS (XRA, BLEO, ETOP), REP | IMR-90, HC A2, WI-38, ti c myo BJ, hepa broblasts | Coppe, Krizhanovsky | |
| MMP-3 | OIS (RAS), DDIS (XRA, BLEO), REP | IMR-90, HCA2, WI-38, BJ | Coppe, Liu, Parrinello | |
| Intermediate increase (2–4 fold) | ||||
| Factor | Senescence inducer | Cell type | Reference | |
| Amphiregulin | OIS (RAS), DDIS (XRA, BLEO) | PrECs, BPH1, RWPE1, PC3, prostate broblasts (PSC27, PSC31, and PSC32) | Coppe, Bavik | |
| ENA-78 | OIS (RAS, MEK), DDIS (XRA) | + | IMR-90, PrECs, BPH1, PC3 | Acosta, Coppe |
| Eotaxin-3 | OIS (RAS), DDIS (XRA), REP | + | IMR-90, HCA2 | Coppe |
| GCP-2 | OIS (RAS), DDIS (XRA) | + | HCA2, PrECs, RWPE1, PC3 | Coppe |
| GITR | OIS (RAS), DDIS (XRA) | HCA2, PrECs, BPH1, RWPE1, PC3 | Coppe | |
| HGF | OIS (RAS), DDIS (XRA, BLEO), REP | IMR-90, HCA2, WI-38, BJ, prostate broblasts (PSC27, PSC31, and PSC32) | Coppe, Bavik, Liu | |
| ICAM-1 | OIS (RAS), DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Rodier, Coppe | |
| IGFBP-2 | DDIS (XRA, BLEO), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3, prostate broblasts (PSC27, PSC31, and PSC32) | Rodier, Coppe, Bavik |
| IGFBP-4 | OIS (RAS), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ | Coppe |
| IGFBP-5 | DDIS (BLEO), REP | + | prostate broblasts (PSC27, PSC31, and PSC32) | Bavik |
| IGFBP-6 | OIS (RAS), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Coppe |
| IL-13 | OIS (RAS), DDIS (XRA), REP | + | IMR-90, WI-38 | Coppe |
| IL-1β | OIS (RAS), DDIS (XRA, BLEO), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Coppe, Liu |
| MCP-4 | OIS (RAS, MEK), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Acosta, Coppe |
| MIF | OIS (RAS), DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Coppe | |
| MIP-3α | OIS (RAS, MEK), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Acosta, Coppe |
| MMP-12 | DDIS (XRA, ETOP) | IMR-90, HCA2, WI-38, BJ, hepatic myo broblasts | Coppe, Krizhanovsky | |
| MMP-13 | DDIS (XRA, ETOP) | IMR-90, HCA2, WI-38, BJ, hepati c myo broblasts | Coppe, Krizhanovsky | |
| MMP-14 | DDIS (XRA) | IMR-90, HCA2, WI-38, BJ | Coppe | |
| NAP2 | OIS (MEK) | IMR-90 | Acosta | |
| Oncostati n M | OIS (MEK), DDIS (XRA) | IMR-90, WI-38 | Acosta, Coppe | |
| Osteoprotegerin | OIS (RAS), DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Rodier, Coppe | |
| PIGF | OIS (RAS), DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Coppe | |
| RANTES | DDIS (BLEO) | HCA2 | Liu | |
| sgp130 | OIS (RAS), DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Rodier, Coppe | |
| TIMP-2 | OIS (RAS), DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Rodier, Coppe | |
| TRAIL-R3 | DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ | Rodier, Coppe | |
| Small increase (below 2 fold) | ||||
| Factor | Senescence inducer | Cell type | Reference | |
| Acrp30 | DDIS (XRA) | PrECs | Coppe | |
| Angiogenin | OIS (RAS), DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Coppe | |
| Axl | DDIS (XRA), REP | WI-38 | Coppe | |
| bFGF | OIS (RAS), DDIS (XRA), REP | IMR-90, HC A2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Coppe | |
| BLC | OIS (RAS) | + | HCA2, BJ | Coppe |
| BTC | DDIS (XRA) | PrECs | Coppe | |
| CTACK | DDIS (XRA) | + | RWPE1, PC3 | Coppe |
| EGF-R | DDIS (XRA) | PrECs, BPH1, PC3 | Coppe | |
| Fas | DDIS (XRA), REP | WI-38 | Coppe | |
| FGF-7 | DDIS (XRA, BLEO), REP | HCA2, WI-38, BJ, prostate broblasts (PSC27, PSC31, and PSC32) | Coppe, Bavik | |
| G-CSF | OIS (RAS) | + | HCA2, BJ | Coppe |
| GDNF | DDIS (XRA) | PrECs | Coppe | |
| HCC-4 | OIS (RAS), DDIS (XRA), REP | + | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Coppe |
| I-309 | OIS(RAS), DDIS (XRA) | + | HCA2 | Coppe |
| IFN-γ | OIS (RAS) | + | HCA2, BJ | Coppe |
| IGFBP-1 | DDIS (XRA), REP | + | HCA2 | Coppe |
| IGFBP-3 | DDIS (XRA, BLEO), REP | + | HCA2, prostate broblasts (PSC27, PSC31, and PSC32) | Rodier, Bavik |
| IL-1 R1 | DDIS (XRA) | HCA2 | Rodier | |
| IL-11 | DDIS (XRA), REP | − | HCA2, BJ | Coppe |
| IL-15 | DDIS (XRA), REP | IMR-90, HCA2, BJ | Coppe | |
| IL-2R-α | DDIS (XRA) | PrECs, PC3 | Coppe | |
| IL-6 R | OIS (RAS), DDIS (XRA) | PrECs, BPH1, RWPE1, PC3 | Coppe | |
| I-TAC | OIS (RAS), DDIS (XRA) | PrECs, BPH1, RWPE1, PC3 | Coppe | |
| Lepti n | DDIS (XRA), REP | IMR-90, HCA2, BJ | Coppe | |
| LIF | OIS (MEK) | IMR-90 | Acosta | |
| MMP-2 | DDIS (BLEO), REP | prostate broblasts (PSC27, PSC31, and PSC32) | Bavik | |
| MSP-a | DDIS (XRA) | RWPE1, PC3 | Coppe | |
| PAI-1 | REP | IMR-90, BJ, JAS-3, HUVEC | West | |
| PAI-2 | REP | IMR-90, BJ, JAS-3 | West | |
| PDGF-BB | DDIS (XRA) | BPH1, RWPE1, PC3 | Coppe | |
| SCF | DDIS (XRA), REP | IMR-90, HCA2, BJ | Coppe | |
| SDF-1 | OIS (RAS), DDIS (XRA) | + | prostate broblasts (PSC27, PSC31, and PSC32) | Bavik |
| sTNF RI | OIS (RAS), DDIS (XRA), REP | − | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Rodier, Coppe |
| sTNF RII | DDIS (XRA), REP | − | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC | 3 Coppe |
| Thrombopoietin | DDIS (XRA) | BPH1, RWPE1, PC3 | Coppe | |
| TIMP-1 | OIS (RAS), DDIS (XRA, BLEO) | HCA2, PrECs, BPH1, PC3, prostate broblasts (PSC27, PSC31, and PSC32) | Coppe, Bavik | |
| tPA | DDIS (BLEO), REP | HCA2, IMR-90, BJ, JAS-3 | West, Liu | |
| uPA | DDIS (BLEO), REP | HCA2, IMR-90, BJ, JAS-3 | West, Liu | |
| uPAR | OIS (RAS), DDIS (XRA), REP | IMR-90, HCA2, WI-38, BJ, PrECs, BPH1, RWPE1, PC3 | Rodier, Coppe | |
| VEGF | OIS (RAS), DDIS (XRA) | PrECs, BPH1, RWPE1, PC3 | Coppe | |