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. 2015 Jul 27;5:158. doi: 10.3389/fonc.2015.00158

Figure 2.

Figure 2

Stromal cell aging and cancer, the senescence-associated secretory phenotype (SASP), and cancer. Age-associated intrinsic and external factors impact stromal fibroblasts and render them senescent. Stromal fibroblasts reactivation leads to subsequent production of different cellular mediators, constituents of the SASP. The figure illustrates different possible outcomes: some SASP components such as the chemokine (CXC2) will contribute to the maintenance of the senescent stromal fibroblast. Production of IL-6, IL-8, extracellular matrix (ECM), and matrix metalloproteinases (MMP)-3 leads to tumor invasion, angiogenesis, tumor growth, tumor remodeling, altered tumor differentiation, and tumor progression. Insulin-like growth factor binding protein (IGFBP7), IL-6, and plasminogen activator inhibitor 1 (PAI-1) trigger cellular senescence, therefore promoting tumor suppression. The production of chromatin assembly factor 1 (CAF1), chemoattractant protein-1 (MCP1), CXC, and IL-15 mediated by innate immune responses leads to tumor clearance (24, 63–68).