liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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
Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Sahlgrens University Hospital, Sweden .
Show others and affiliations
2013 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 29, 124-135 p.Article in journal (Refereed) Published
Abstract [en]

It is well-established that prostaglandins (PGs) affect tumorigenesis, and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexia–cachexia syndrome, in malignant cancer. However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia–cachexia is unknown. Here, we addressed this issue by transplanting mice with a tumor that elicits anorexia. Meal pattern analysis revealed that the anorexia in the tumor-bearing mice was due to decreased meal frequency. Treatment with a non-selective COX inhibitor attenuated the anorexia, and also tumor growth. When given at manifest anorexia, non-selective COX-inhibitors restored appetite and prevented body weight loss without affecting tumor size. Despite COX-2 induction in the cerebral blood vessels of tumor-bearing mice, a selective COX-2 inhibitor had no effect on the anorexia, whereas selective COX-1 inhibition delayed its onset. Tumor growth was associated with robust increase of PGE2 levels in plasma – a response blocked both by non-selective COX-inhibition and by selective COX-1 inhibition, but not by COX-2 inhibition. However, there was no increase in PGE2-levels in the cerebrospinal fluid. Neutralization of plasma PGE2 with specific antibodies did not ameliorate the anorexia, and genetic deletion of microsomal PGE synthase-1 (mPGES-1) affected neither anorexia nor tumor growth. Furthermore, tumor-bearing mice lacking EP4 receptors selectively in the nervous system developed anorexia. These observations suggest that COX-enzymes, most likely COX-1, are involved in cancer-elicited anorexia and weight loss, but that these phenomena occur independently of host mPGES-1, PGE2 and neuronal EP4 signaling.

Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 29, 124-135 p.
Keyword [en]
Cancer anorexia-cachexia, Cyclooxygenase, Microsomal prostaglandin E synthase-1, Prostaglandin E2
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-90188DOI: 10.1016/j.bbi.2012.12.020ISI: 000315365400013OAI: oai:DiVA.org:liu-90188DiVA: diva2:612377
Note

Funding Agencies|Swedish Cancer Foundation||Swedish Research Council||Swedish Brain Foundation||

Available from: 2013-04-04 Created: 2013-03-21 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Mechanisms Behind Illness-Induced Anorexia
Open this publication in new window or tab >>Mechanisms Behind Illness-Induced Anorexia
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Loss of appetite is together with fever and malaise hallmarks of infection. Loosing appetite during an acute infection such as influenza does not result in any longlasting effects, but loosing appetite during chronic diseases such as cancer or AIDS constitutes a risk factor for mortality. Food intake regulation during inflammation is orchestrated by the brain in response to peripheral inflammatory signals. It is known that expression of the prostaglandin synthesizing enzyme cyclooxygenase 2 (COX-2) is crucial for the mechanisms underlying inflammation-induced anorexia, and that prostaglandin E2 (PGE2) is involved in anorexia induced by interleukin-1 beta (IL-1β). In this thesis I examined the prostaglandin-pathways proposed to be involved in anorexia. We show that acute anorexia is dependent on COX-2 expression, while cancer-induced anorexia is mediated by cyclooxygenase 1 (COX-1), at least in the initial stages, suggesting that the signaling pathways for chronic- and acute anorexia are distinct. We were able to demonstrate that the pathway underlying acute anorexia is distinct from that of fever, and that taste aversion is prostaglandin independent. We could also show that both acute and chronic anorexia-cachexia is dependent on expression of myeloid differentiation primary response gene (MyD88) in hematopoietic/myeloid cells.

In summary, the findings presented in this thesis suggest that anorexia is a result of many different signaling pathways, as opposed to what is the case for several other inflammatory symptoms such as fever and malaise, where the pathways have been shown to be very exclusive. This provides new insight into the diversity of the pathways underlying inflammatory symptoms, which is fundamental for the ability to present potential, symptom-specific drug targets.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 79 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1549
National Category
Cell and Molecular Biology Neurosciences
Identifiers
urn:nbn:se:liu:diva-132640 (URN)10.3384/diss.diva-132640 (DOI)9789176856482 (ISBN)
Public defence
2016-12-09, Berzeliussalen, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2017-06-14Bibliographically approved

Open Access in DiVA

fulltext(1135 kB)682 downloads
File information
File name FULLTEXT01.pdfFile size 1135 kBChecksum SHA-512
17644d4f1bfbacab10ebbb303f008c12a1b3cbd1ae4ceb51fe2363f4d2c157d67f1a508d16b9ce0083d22f039174f58b17838fc445902631b05adeba99d5568b
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Authority records BETA

Ruud, JohanNilsson, AnnaEngström Ruud, LindaNilsberth, CamillaEngblom, DavidBlomqvist, Anders

Search in DiVA

By author/editor
Ruud, JohanNilsson, AnnaEngström Ruud, LindaNilsberth, CamillaEngblom, DavidBlomqvist, Anders
By organisation
Cell BiologyFaculty of Health Sciences
In the same journal
Brain, behavior, and immunity
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 682 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
urn-nbn

Altmetric score

doi
urn-nbn
Total: 193 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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