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Sökning: onr:"swepub:oai:lup.lub.lu.se:914a3af7-86e6-41ff-a4e4-c690a6c35da4" > Cancer-Associated F...

Cancer-Associated Fibroblasts Expressing CXCL14 Rely upon NOS1-Derived Nitric Oxide Signaling for Their Tumor-Supporting Properties

Augsten, Martin (författare)
Sjoberg, Elin (författare)
Frings, Oliver (författare)
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Vorrink, Sabine U. (författare)
Frijhoff, Jeroen (författare)
Olsson, Eleonor, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Division V, Onkologi och Patologi, MV, Oncology and Pathology, MV
Borg, Åke, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Division V, Onkologi och Patologi, MV, Oncology and Pathology, MV, Strategiska forskningsområden, Strategic Research Areas, BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation, BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Ostman, Arne (författare)
Borg, A (författare)
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Lunds universitet Onkologi och Patologi, MV. (creator_code:org_t)
Lunds universitet BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation. (creator_code:org_t)
2014
Engelska.
Ingår i: Cancer Research. - American Association for Cancer Research Inc.. - 1538-7445. ; 74:11, s. 2999-3010
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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 HIF1 alpha 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. (C) 2014 AACR.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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