Stromal resistance of fibroblasts against oxidative damage: involvement of tumor cell-secreted platelet-derived growth factor (PDGF) and phosphoinositide 3-kinase (PI3K) activation.
A critical step in tumor progression is the interaction of malignant and stromal cells via paracrine mechanisms. Stromal cells, particularly fibroblasts, support cancer cells in invasion of the surrounding tissue for access to the vascular system. Here, the question is addressed of whether tumor cells induce 'stromal resistance', i.e. protect the microenvironment from oxidative damage. The supernatant of cultured skin-derived tumor cells was added to fibroblasts and was shown to protect the fibroblasts from hydrogen peroxide-mediated cell toxicity. The platelet-derived growth factor secreted from the cancer cells was identified as trigger of this protection in fibroblasts via the phosphoinositide 3-kinase pathway. These data suggest that prosurvival signals in stromal fibroblasts as initiated by tumor cells constitute a strategy of 'stromal resistance', illustrating a novel biological role of fibroblasts for the tumor microenvironment.
Werth
Christel
C
Institute of Biochemistry and Molecular Biology I, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
Stuhlmann
Dominik
D
Cat
Bahar
B
Steinbrenner
Holger
H
Alili
Lirija
L
Sies
Helmut
H
Brenneisen
Peter
P
D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D000975:Antioxidants; D010982:Platelet-Derived Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt