Stromal fibroblasts synergize with hypoxic oxidative stress to enhance melanoma aggressiveness.
On the basis of recent advances indicating a key role of microenvironment for tumor progression, we investigated the role of fibroblasts, macrophages and hypoxia, for primary melanoma aggressiveness. Our data indicate a key role of hypoxia in stromal reactivity, acting on both myofibroblasts and machrophages differentiation. Hypoxic myofibroblasts are more active than macrophages in inducing melanoma invasiveness and exploit their oxidative stress due to hypoxia to secrete soluble factors favouring melanoma invasion and chemotaxis. We underscore the key role of microenviroment on melanoma malignancy, highlighting reactive fibroblasts, intratumoral hypoxia and oxidative stress as promising targets for melanoma antimetastatic strategies.
Department of Biochemical Sciences, University of Florence, Tuscany Tumor Institute and Center for Research, Transfer and High Education DenoTHE, 50134 Florence, Italy.
Giuseppina
G
Comito
Elisa
E
Giannoni
Paola
P
Di Gennaro
Coral Pons
CP
Segura
Gianni
G
Gerlini
Paola
P
Chiarugi
D015687:Cell Hypoxia; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D012867:Skin / Q000166:cytology; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D016207:Cytokines; D015850:Interleukin-6; D017382:Reactive Oxygen Species; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A