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  EDA-Fibronectin Originating from Osteoblasts Inhibits the Immune Response against Cancer

Rossnagl, S., Altrock, E., Sens, C., Kraft, S., Rau, K., Milsom, M. D., et al. (2016). EDA-Fibronectin Originating from Osteoblasts Inhibits the Immune Response against Cancer. PLoS Biology, 14(9): e1002562. doi:10.1371/journal.pbio.1002562.

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 Creators:
Rossnagl, Stephanie1, Author              
Altrock, Eva1, Author              
Sens, Carla1, Author              
Kraft, Sabrina1, Author              
Rau, Katrin1, Author              
Milsom, Michael D.2, Author
Giese, Thomas2, Author
Samstag, Yvonne2, Author
Nakchbandi, Inaam A.1, Author              
Affiliations:
1Nakchbandi, Inaam / Translational Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565162              
2external, ou_persistent22              

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Free keywords: HUMAN HEMATOPOIETIC PROGENITORS; SOLUBLE INTERLEUKIN-6 RECEPTOR; STEM-CELL NICHES; SUPPRESSOR-CELLS; BONE-MARROW; IN-VIVO; LIVER FIBROSIS; T-LYMPHOCYTES; INTEGRIN EXPRESSION; ALPHA-4 INTEGRINSBiochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics;
 Abstract: Osteoblasts lining the inner surface of bone support hematopoietic stem cell differentiation by virtue of proximity to the bone marrow. The osteoblasts also modify their own differentiation by producing various isoforms of fibronectin (FN). Despite evidence for immune regulation by osteoblasts, there is limited knowledge of how osteoblasts modulate cells of the immune system. Here, we show that extra domain A (EDA)-FN produced by osteoblasts increases arginase production in myeloid-derived cells, and we identify alpha 5 beta 1 as the mediating receptor. In different mouse models of cancer, osteoblasts or EDA-FN was found to upregulate arginase-1 expression in myeloid-derived cells, resulting in increased cancer growth. This harmful effect can be reduced by interfering with the integrin alpha 5 beta 1 receptor or inhibiting arginase. Conversely, in tissue injury, the expression of arginase-1 is normally beneficial as it dampens the immune response to allow wound healing. We show that EDA-FN protects against excessive fibrotic tissue formation in a liver fibrosis model. Our results establish an immune regulatory function for EDA-FN originating from the osteoblasts and identify new avenues for enhancing the immune reaction against cancer.

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Language(s): eng - English
 Dates: 2016-09-21
 Publication Status: Published online
 Pages: 32
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Title: PLoS Biology
  Other : PLoS Biol.
Source Genre: Journal
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Publ. Info: Public Library of Science
Pages: - Volume / Issue: 14 (9) Sequence Number: e1002562 Start / End Page: - Identifier: ISSN: 1544-9173
CoNE: https://pure.mpg.de/cone/journals/resource/111056649444170