Walker 256 tumor‐bearing rats demonstrate altered interstitial cells of Cajal. Effects on ICC in the Walker 256 tumor model

Background Cachexia is a significant problem in patients with cancer. The effect of cancer on interstitial cells of Cajal (ICC) and neurons of the gastrointestinal tract have not been studied previously. Although supplementation with L‐glutamine 2% may have beneficial effects in cancer‐related cache...

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Published in:Neurogastroenterology and motility 2016-01, Vol.28 (1), p.101-115
Main Authors: Fracaro, L., Frez, F. C. V., Silva, B. C., Vicentini, G. E., Souza, S. R. G., Martins, H. A., Linden, D. R., Guarnier, F. A., Zanoni, J. N.
Format: Article
Language:English
Subjects:
Animals
Anoctamin-1
antioxidants
Blotting, Western
Cachexia - metabolism
Cancer
Carcinoma 256, Walker - metabolism
Carcinoma 256, Walker - pathology
Chloride Channels - drug effects
Chloride Channels - metabolism
enteric nervous system
Glutamine - pharmacology
Immunohistochemistry
Interstitial Cells of Cajal - drug effects
Interstitial Cells of Cajal - metabolism
intestinal motility
Jejunum - drug effects
Male
Myenteric Plexus - cytology
Myenteric Plexus - drug effects
Nitric Oxide Synthase Type I - drug effects
Nitric Oxide Synthase Type I - metabolism
Oxidative Stress - drug effects
Rats
Rats, Wistar
Rodents
Tumor Burden
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Summary:Background Cachexia is a significant problem in patients with cancer. The effect of cancer on interstitial cells of Cajal (ICC) and neurons of the gastrointestinal tract have not been studied previously. Although supplementation with L‐glutamine 2% may have beneficial effects in cancer‐related cachexia, and be protective of ICC in models of oxidative stress such as diabetes, its effects on ICC in cancer have also not been studied. Methods Twenty‐eight male Wistar rats were divided into four groups: control (C), control supplemented with L‐glutamine (CG), Walker 256 tumor (WT), and Walker 256 tumor supplemented with L‐glutamine (WTG). Rats were implanted with tumor cells or injected with saline in the right flank. After 14 days, the jejunal tissues were collected and processed for immunohistochemical techniques including whole mounts and cryosections and Western blot analysis. Key Results Tumor‐bearing rats demonstrate reduced numbers of Myenteric ICC and deep muscular plexus ICC and yet increased Ano1 protein expression and enhanced ICC networks. In addition, there is more nNOS protein expressed in tumor‐bearing rats compared to controls. L‐glutamine treatment had a variety of effects on ICC that may be related to the disease state and the interaction of ICC and nNOS neurons. Regardless, L‐glutamine reduced the size of tumors and also tumor‐induced cachexia that was not due to altered food intake. Conclusions & Inferences There are significant effects on ICC in the Walker 256 tumor model. Although supplementation with L‐glutamine has differential and complex effects of ICC, it reduces tumor size and tumor‐associated cachexia, which supports its beneficial therapeutic role in cancer. Tumor‐bearing rats demonstrate reduced numbers of ICC‐MY and ICC‐DMP and yet increased Ano1 protein expression and enhanced ICC networks. In addition, there is more nNOS protein expressed in tumor‐bearing rats compared to controls. L‐glutamine treatment had a variety of effects on ICC that may be related to the disease state and the interaction of ICC and nNOS neurons. Regardless, L‐glutamine reduced the size of tumors and also tumor‐induced cachexia that was not due to altered food intake.
ISSN:1350-1925
1365-2982
DOI:10.1111/nmo.12702