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Extrinsic intestinal denervation modulates tumor development in the small intestine of Apc(Min/+) mice.

Liu V, Dietrich A, Kasparek MS, Benhaqi P, Schneider MR, Schemann M, Seeliger H, Kreis ME - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: Chronic intestinal inflammation is associated with increased risk of colorectal cancer.We aimed to study potential extrinsic neuronal modulation of intestinal tumor development in a mouse model.Experiments were performed with male Apc(Min/+) or wild type mice (4 weeks old, body weight approximately 20 g).

View Article: PubMed Central - PubMed

Affiliation: Department of General-, Visceral- and Vascular Surgery, Charité University Medicine, Campus Benjamin Franklin, Hindenburgdamm 30, D-12000, Berlin, Germany. verena.liu@charite.de.

ABSTRACT

Background: Innervation interacts with enteric immune responses. Chronic intestinal inflammation is associated with increased risk of colorectal cancer. We aimed to study potential extrinsic neuronal modulation of intestinal tumor development in a mouse model.

Methods: Experiments were performed with male Apc(Min/+) or wild type mice (4 weeks old, body weight approximately 20 g). Subgroups with subdiaphragmatic vagotomy (apcV/wtV), sympathetic denervation of the small intestine (apcS/wtS) or sham operated controls (apcC/wtC) were investigated (n = 6-14 per group). Three months after surgical manipulation, 10 cm of terminal ileum were excised, fixed for 48 h in 4% paraformaldehyde and all tumors were counted and their area determined in mm(2) (mean ± standard error of the mean (SEM)). Whole mounts of the muscularis of terminal ileum and duodenum (internal positive control) were also stained for tyrosine hydroxylase to confirm successful sympathetic denervation.

Results: Tumor count in Apc(Min/+) mice was 62 ± 8 (apcC), 46 ± 11 (apcV) and 54 ± 8 (apcS) which was increased compared to wildtype controls with 4 ± 0.5 (wtC), 5 ± 0.5 (wtV) and 5 ± 0.6 (wtS; all p < 0.05). For Apc(Min/+) groups, vagotomized animals showed a trend towards decreased tumor counts compared to sham operated Apc(Min/+) controls while sympathetic denervation was similar to sham Apc(Min/+). Area covered by tumors in Apc(Min/+) mice was 55 ± 10 (apcC), 31 ± 8 (apcV) and 42 ± 8 (apcS) mm(2), which was generally increased compared to wildtype controls with 7 ± 0.6 (wtC), 7 ± 0.4 (wtV) and 7 ± 0.6 (wtS) mm(2) (all p < 0.05). In Apc(Min/+) groups, tumor area was decreased in vagotomized animals compared to sham operated controls (p < 0.05) while sympathetically denervated mice showed a minor trend to decreased tumor area compared to controls.

Conclusions: Extrinsic innervation of the small bowel is likely to modulate tumor development in Apc(Min/+) mice. Interrupted vagal innervation, but not sympathetic denervation, seems to inhibit tumor growth.

No MeSH data available.


Related in: MedlinePlus

Area covered by tumor in the terminal ileum. Tumor area was determined in a 10 cm segment of terminal ileum in ApcMin/+ mice and wt animals after sham operation, vagotomy and complete mesenteric denervation. Data are mean ± SEM. P < 0.05 for ApcMin/+ vs. wt (*) and for APC sham vs. APC vagotomy (§).
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Fig5: Area covered by tumor in the terminal ileum. Tumor area was determined in a 10 cm segment of terminal ileum in ApcMin/+ mice and wt animals after sham operation, vagotomy and complete mesenteric denervation. Data are mean ± SEM. P < 0.05 for ApcMin/+ vs. wt (*) and for APC sham vs. APC vagotomy (§).

Mentions: The area covered by tumors in the 10 cm segment of terminal ileum in wildtype controls was 7 ± 0.6 mm2 following sham operation, 7 ± 0.4 mm2 after subdiaphragmatic vagotomy, and 7 ± 0.6 mm2 in animals having undergone denervation at the level of the superior mesenteric artery (Figure 5). The tumor area was increased in ApcMin/+ mice compared to corresponding wild type animals (all p < 0.05). In ApcMin/+ mice, corresponding areas covered by tumors were 54 ± 11 mm2 following sham operation, 30 ± 8 mm2 after subdiaphragmatic vagotomy, and 42 ± 8 mm2 following denervation at the superior mesenteric artery. In ApcMin/+ groups, tumor area was decreased in vagotomized animals compared to sham controls (p < 0.05), while mice denervated at the superior mesenteric artery were not different but showed a minor trend to decreased tumor area compared to sham operated controls.Figure 5


Extrinsic intestinal denervation modulates tumor development in the small intestine of Apc(Min/+) mice.

Liu V, Dietrich A, Kasparek MS, Benhaqi P, Schneider MR, Schemann M, Seeliger H, Kreis ME - J. Exp. Clin. Cancer Res. (2015)

Area covered by tumor in the terminal ileum. Tumor area was determined in a 10 cm segment of terminal ileum in ApcMin/+ mice and wt animals after sham operation, vagotomy and complete mesenteric denervation. Data are mean ± SEM. P < 0.05 for ApcMin/+ vs. wt (*) and for APC sham vs. APC vagotomy (§).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4440557&req=5

Fig5: Area covered by tumor in the terminal ileum. Tumor area was determined in a 10 cm segment of terminal ileum in ApcMin/+ mice and wt animals after sham operation, vagotomy and complete mesenteric denervation. Data are mean ± SEM. P < 0.05 for ApcMin/+ vs. wt (*) and for APC sham vs. APC vagotomy (§).
Mentions: The area covered by tumors in the 10 cm segment of terminal ileum in wildtype controls was 7 ± 0.6 mm2 following sham operation, 7 ± 0.4 mm2 after subdiaphragmatic vagotomy, and 7 ± 0.6 mm2 in animals having undergone denervation at the level of the superior mesenteric artery (Figure 5). The tumor area was increased in ApcMin/+ mice compared to corresponding wild type animals (all p < 0.05). In ApcMin/+ mice, corresponding areas covered by tumors were 54 ± 11 mm2 following sham operation, 30 ± 8 mm2 after subdiaphragmatic vagotomy, and 42 ± 8 mm2 following denervation at the superior mesenteric artery. In ApcMin/+ groups, tumor area was decreased in vagotomized animals compared to sham controls (p < 0.05), while mice denervated at the superior mesenteric artery were not different but showed a minor trend to decreased tumor area compared to sham operated controls.Figure 5

Bottom Line: Chronic intestinal inflammation is associated with increased risk of colorectal cancer.We aimed to study potential extrinsic neuronal modulation of intestinal tumor development in a mouse model.Experiments were performed with male Apc(Min/+) or wild type mice (4 weeks old, body weight approximately 20 g).

View Article: PubMed Central - PubMed

Affiliation: Department of General-, Visceral- and Vascular Surgery, Charité University Medicine, Campus Benjamin Franklin, Hindenburgdamm 30, D-12000, Berlin, Germany. verena.liu@charite.de.

ABSTRACT

Background: Innervation interacts with enteric immune responses. Chronic intestinal inflammation is associated with increased risk of colorectal cancer. We aimed to study potential extrinsic neuronal modulation of intestinal tumor development in a mouse model.

Methods: Experiments were performed with male Apc(Min/+) or wild type mice (4 weeks old, body weight approximately 20 g). Subgroups with subdiaphragmatic vagotomy (apcV/wtV), sympathetic denervation of the small intestine (apcS/wtS) or sham operated controls (apcC/wtC) were investigated (n = 6-14 per group). Three months after surgical manipulation, 10 cm of terminal ileum were excised, fixed for 48 h in 4% paraformaldehyde and all tumors were counted and their area determined in mm(2) (mean ± standard error of the mean (SEM)). Whole mounts of the muscularis of terminal ileum and duodenum (internal positive control) were also stained for tyrosine hydroxylase to confirm successful sympathetic denervation.

Results: Tumor count in Apc(Min/+) mice was 62 ± 8 (apcC), 46 ± 11 (apcV) and 54 ± 8 (apcS) which was increased compared to wildtype controls with 4 ± 0.5 (wtC), 5 ± 0.5 (wtV) and 5 ± 0.6 (wtS; all p < 0.05). For Apc(Min/+) groups, vagotomized animals showed a trend towards decreased tumor counts compared to sham operated Apc(Min/+) controls while sympathetic denervation was similar to sham Apc(Min/+). Area covered by tumors in Apc(Min/+) mice was 55 ± 10 (apcC), 31 ± 8 (apcV) and 42 ± 8 (apcS) mm(2), which was generally increased compared to wildtype controls with 7 ± 0.6 (wtC), 7 ± 0.4 (wtV) and 7 ± 0.6 (wtS) mm(2) (all p < 0.05). In Apc(Min/+) groups, tumor area was decreased in vagotomized animals compared to sham operated controls (p < 0.05) while sympathetically denervated mice showed a minor trend to decreased tumor area compared to controls.

Conclusions: Extrinsic innervation of the small bowel is likely to modulate tumor development in Apc(Min/+) mice. Interrupted vagal innervation, but not sympathetic denervation, seems to inhibit tumor growth.

No MeSH data available.


Related in: MedlinePlus