Refereed journal article or data article (A1)

Blocking activin receptor ligands is not sufficient to rescue cancer-associated gut microbiota - a role for gut microbial flagellin in colorectal cancer and cachexia?




List of AuthorsSatu Pekkala, Anniina Keskitalo, Emilia Kettunen, Sanna Lensu, Noora Nykänen, Teijo Kuopio, Olli Ritvos, Jaakko Hentilä, Tuuli A. Nissinen, Juha J. Hulmi

PublisherMDPI

Publication year2019

JournalCancers

Volume number11

Issue number11

Number of pages23

DOIhttp://dx.doi.org/10.3390/cancers11111799

URLhttps://www.mdpi.com/2072-6694/11/11/1799/htm

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/42787973


Abstract

Colorectal 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.


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Last updated on 2022-07-04 at 17:31