Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The combined action of mast cell chymase, tryptase and carboxypeptidase A3 protects against melanoma colonization of the lung
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Univ Copenhagen, Dept Immunol & Microbiol, Copenhagen, Denmark..
Show others and affiliations
2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 15, p. 25066-25079Article in journal (Refereed) Published
Abstract [en]

Mast cell secretory granules are densely packed with various bioactive mediators including proteases of chymase, tryptase and CPA3 type. Previous studies have indicated that mast cells can affect the outcome of melanoma but the contribution of the mast cell granule proteases to such effects has not been clear. Here we addressed this issue by assessing mice lacking either the chymase Mcpt4, the tryptase Mcpt6 or carboxypeptidase A3 (Cpa3), as well as mice simultaneously lacking all three proteases, in a model of melanoma dissemination from blood to the lung. Although mice with individual deficiency in the respective proteases did not differ significantly from wildtype mice in the extent of melanoma colonization, mice with multiple protease deficiency (Mcpt4/Mcpt6/Cpa3-deficient) exhibited a higher extent of melanoma colonization in lungs as compared to wildtype animals. This was supported by higher expression of melanoma-specific genes in lungs of Mcpt4/Mcpt6/CPA3-deficient vs. wildtype mice. Cytokine profiling showed that the levels of CXCL16, a chemokine with effects on T cell populations and NKT cells, were significantly lower in lungs of Mcpt4/Mcpt6/Cpa3-deficient animals vs. controls, suggesting that multiple mast cell protease deficiency might affect T cell or NKT cell populations. In line with this, we found that the Mcpt4/Mcpt6/Cpa3-deficiency was associated with a reduction in cells expressing CD1d, a MHC class 1-like molecule that is crucial for presenting antigen to invariant NKT (iNKT) cells. Together, these findings indicate a protective role of mast cell-specific proteases in melanoma dissemination, and suggest that this effect involves a CXCL16/CD1d/NKT cell axis.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2017. Vol. 8, no 15, p. 25066-25079
Keywords [en]
mast cells, chymase, tryptase, carboxypeptidase A3, CD1d
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-322187DOI: 10.18632/oncotarget.15339ISI: 000399340300085PubMedID: 28212574OAI: oai:DiVA.org:uu-322187DiVA, id: diva2:1096087
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Heart Lung FoundationSwedish Research Council FormasTorsten Söderbergs stiftelseAvailable from: 2017-05-17 Created: 2017-05-17 Last updated: 2018-01-13Bibliographically approved

Open Access in DiVA

fulltext(5755 kB)86 downloads
File information
File name FULLTEXT01.pdfFile size 5755 kBChecksum SHA-512
5c5c722d857eadaa21e0a9caa70c63d635c748d141bfcfe1c32878a27328bf1859a59443edac561cc9fcb6025bb7917d965edfca6f571c7ae27ecab686bfc960
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Grujic, MirjanaPaivandy, AidaGustafson, Ann-MarieÖhrvik, HelenaPejler, Gunnar
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
OncoTarget
Cancer and OncologyCell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 86 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 438 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf