Skip to Content
Merck
  • Cancer-associated fibroblasts expressing CXCL14 rely upon NOS1-derived nitric oxide signaling for their tumor-supporting properties.

Cancer-associated fibroblasts expressing CXCL14 rely upon NOS1-derived nitric oxide signaling for their tumor-supporting properties.

Cancer research (2014-04-09)
Martin Augsten, Elin Sjöberg, Oliver Frings, Sabine U Vorrink, Jeroen Frijhoff, Eleonor Olsson, Åke Borg, Arne Östman
ABSTRACT

Cancer-associated fibroblasts (CAF) stimulate tumor growth and metastasis. Signals supporting CAF function are thus emerging as candidate therapeutic targets in the tumor microenvironment. The chemokine CXCL14 is a potent inducer of CAF protumorigenic functions. This study is aimed at learning how the protumoral functions of CXCL14-expressing CAF are maintained. We found that the nitric oxide synthase NOS1 is upregulated in CXCL14-expressing CAF and in fibroblasts stimulated with CXCL14. Induction of Nos1 was associated with oxidative stress and occurred together with activation of NRF2 and HIF1α signaling in CXCL14-expressing CAF. Genetic or pharmacologic inhibition of NOS1 reduced the growth of CXCL14-expressing fibroblasts along with their ability to promote tumor formation following coinjection with prostate or breast cancer cells. Tumor analysis revealed reduced macrophage infiltration, with NOS1 downregulation in CXCL14-expressing CAF and lymphangiogenesis as a novel component of CXCL14-promoted tumor growth. Collectively, our findings defined key components of a signaling network that maintains the protumoral functions of CXCL14-stimulated CAF, and they identified NOS1 as intervention target for CAF-directed cancer therapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrogen peroxide solution, tested according to Ph. Eur.
Supelco
Hydrogen peroxide solution, ≥30%, for trace analysis
Sigma-Aldrich
Hydrogen peroxide solution, 34.5-36.5%
Sigma-Aldrich
Hydrogen peroxide solution, 30 % (w/w) in H2O, contains stabilizer
Supelco
Hydrogen peroxide solution, 30 % (w/w), for ultratrace analysis
Millipore
Hydrogen peroxide solution, 3%, suitable for microbiology
Sigma-Aldrich
Hydrogen peroxide solution, contains ~200 ppm acetanilide as stabilizer, 3 wt. % in H2O
Sigma-Aldrich
Anti-Nitrotyrosine Antibody, clone 1A6, clone 1A6, Upstate®, from mouse
Supelco
Glutathione, Pharmaceutical Secondary Standard; Certified Reference Material
Glutathione, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 30 wt. % in H2O, meets USP testing specifications
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 30 wt. % in H2O, ACS reagent
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 35 wt. % in H2O
Sigma-Aldrich
Hydrogen peroxide solution, purum p.a., ≥35% (RT)
Sigma-Aldrich
Hydrogen Peroxide Solution, 30% (w/w), puriss. p.a., reag. ISO, reag. Ph. Eur.
Sigma-Aldrich
Hydrogen peroxide solution, 50 wt. % in H2O, stabilized
Sigma-Aldrich
2,3-Dimethoxy-1,4-naphthoquinone, ≥99%, solid
Sigma-Aldrich
L-Glutathione reduced, BioXtra, ≥98.0%
Sigma-Aldrich
L-Glutathione reduced, suitable for cell culture, BioReagent, ≥98.0%, powder
Sigma-Aldrich
L-Glutathione reduced, ≥98.0%