Figure 3.2.

Oxidative stress activates stroma fibroblasts. In breast cancer, under oxidative stress, stroma-associated fibroblasts acquire an activated state and can be identified by numerous markers including α-smooth muscle actin (α-SMA), fibroblast specific protein (FSP), fibroblast activation protein (FAP), PDGF receptors-β, desmin, endosialin, tenascin-c, palladin, vimentin, pro-collagen, stromelysin-3, and cadherin-11. Oxidative stress can cause cell senescence, locking activated fibroblast in a nonproliferative state and creating a senescence-associated secretory phenotype, which manifests in releasing factors that affect neighboring cells. Activation of fibroblasts, followed by secretion of numerous factors including metalloproteinases (MMP-2, MMP-3, MMP9), growth factors (HGF-2, EGF, IGF, TGFβ, VEGF), the polysaccharide hyaluronan and tenascin-c significantly promotes proliferation and growth of premalignant epithelial cells and cancer cells, invasiveness, metastasis, and angiogenesis in breast cancer. (See Page 2 in Color Section at the back of the book.)