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dc.contributor.authorPekkala, Satu
dc.contributor.authorKeskitalo, Anniina
dc.contributor.authorKettunen, Emilia
dc.contributor.authorLensu, Sanna
dc.contributor.authorNykänen, Noora
dc.contributor.authorKuopio, Teijo
dc.contributor.authorRitvos, Olli
dc.contributor.authorHentilä, Jaakko
dc.contributor.authorNissinen, Tuuli A.
dc.contributor.authorHulmi, Juha J.
dc.date.accessioned2019-11-20T11:22:42Z
dc.date.available2019-11-20T11:22:42Z
dc.date.issued2019
dc.identifier.citationPekkala, Satu; Keskitalo, Anniina; Kettunen, Emilia; Lensu, Sanna; Nykänen, Noora; Kuopio, Teijo; Ritvos, Olli; Hentilä, Jaakko; Nissinen, Tuuli A.; Hulmi, Juha J. (2019). Blocking Activin Receptor Ligands Is Not Sufficient to Rescue Cancer-Associated Gut Microbiota : A Role for Gut Microbial Flagellin in Colorectal Cancer and Cachexia?. Cancers, 11 (11), 1799. DOI: 10.3390/cancers11111799
dc.identifier.otherCONVID_33579478
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/66448
dc.description.abstractColorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. Further, we examined the possible relationship between the microbial surface molecule flagellin and CRC. CRC cells (C26) were inoculated into mice. Activin receptor (ACVR) ligands were blocked, either before tumor formation or before and after, to increase muscle mass and prevent muscle loss. The effects of flagellin on C26-cells were studied in vitro. The occurrence of similar phenomena were studied in murine and human tumors. Cancer modulated the gut microbiota without consistent effects of blocking the ACVR ligands. However, continued treatment for muscle loss modified the association between microbiota and weight loss. Several abundant microbial taxa in cancer were flagellated. Exposure of C26-cells to flagellin increased IL6 and CCL2/MCP-1 mRNA and IL6 excretion. Murine C26 tumors expressed more IL6 and CCL2/MCP-1 mRNA than C26-cells, and human CRC tumors expressed more CCL2/MCP-1 than healthy colon sites. Additionally, flagellin decreased caspase-1 activity and the production of reactive oxygen species, and increased cytotoxicity in C26-cells. Conditioned media from flagellin-treated C26-cells deteriorated C2C12-myotubes and decreased their number. In conclusion, cancer increased flagellated microbes that may promote CRC survival and cachexia by inducing inflammatory proteins such as MCP-1. Cancer-associated gut microbiota could not be rescued by blocking ACVR ligands.en
dc.format.mimetypeapplication/pdf
dc.languageeng
dc.publisherMDPI AG
dc.relation.ispartofseriesCancers
dc.rightsCC BY 4.0
dc.subject.otherinflammation
dc.subject.otheractivin
dc.subject.othermyostatin
dc.subject.othermicrobiome
dc.subject.otherIL6
dc.subject.otherCCL2
dc.subject.otherMCP-1
dc.titleBlocking Activin Receptor Ligands Is Not Sufficient to Rescue Cancer-Associated Gut Microbiota : A Role for Gut Microbial Flagellin in Colorectal Cancer and Cachexia?
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201911204953
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.relation.issn2072-6694
dc.relation.numberinseries11
dc.relation.volume11
dc.type.versionpublishedVersion
dc.rights.copyright© 2019 by the authors
dc.rights.accesslevelopenAccessfi
dc.relation.grantnumber275922
dc.relation.grantnumber308042
dc.subject.ysopaksusuolisyöpä
dc.subject.ysotulehdus
dc.subject.ysoproteiinit
dc.subject.ysolihassurkastumasairaudet
dc.subject.ysosuolistomikrobisto
dc.subject.ysoligandit
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p5937
jyx.subject.urihttp://www.yso.fi/onto/yso/p1049
jyx.subject.urihttp://www.yso.fi/onto/yso/p4332
jyx.subject.urihttp://www.yso.fi/onto/yso/p15977
jyx.subject.urihttp://www.yso.fi/onto/yso/p37925
jyx.subject.urihttp://www.yso.fi/onto/yso/p24741
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.3390/cancers11111799
dc.relation.funderSuomen Akatemiafi
dc.relation.funderSuomen Akatemiafi
dc.relation.funderAcademy of Finlanden
dc.relation.funderAcademy of Finlanden
jyx.fundingprogramAkatemiatutkijan tehtävä, SAfi
jyx.fundingprogramAkatemiatutkijan tehtävä, SAfi
jyx.fundingprogramResearch post as Academy Research Fellow, AoFen
jyx.fundingprogramResearch post as Academy Research Fellow, AoFen
jyx.fundinginformationThis work was funded by the Academy of Finland (Grant No. 308042 to S.P. and 275922 to J.J.H.) and by the Cancer Society of Finland to J.J.H.


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