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The effect of SCF and ouabain on small intestinal motility dysfunction induced by gastric cancer peritoneal metastasis

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Abstract

The interstitial cells of Cajal (ICCs) play an important role in maintaining the normal function of gastrointestinal dynamics. In our previous study, we reported that, in advanced gastric cancer, the frequency of bowel movement is always reduced, due in part to the decreased number of ICCs. To investigate the impact of ICCs in gastric cancer, we established a mouse model of gastric cancer peritoneal metastasis using SGC-7901 gastric adenocarcinoma cells and their supernatant. Then, stem cell factor (SCF) and ouabain were used as therapeutic agents to improve gut dynamics. Our data showed that, compared with the normal mice, treatment with SGC-7901 cells and their supernatant led to a significant reduction of the muscle layer thickness, a decreased number of ICCs, broadened gaps between ICCs and surrounding cells, degeneration and necrosis of smooth muscle cells (SMCs), and infiltration of inflammatory cells. In contrast to SGC-7901 cell and supernatant treatment, SCF intervention caused mild submucosal edema and mitochondrial proliferation in the ICCs and SMCs. Additionally, ouabain treatment led to inflammatory cells infiltration into the submucosa and a decreased volume of ICCs. In conclusion, our data illustrated that, under the condition of gastric cancer peritoneal metastasis, the dysfunction of intestinal peristalsis may be related to pathological changes in ICCs. Moreover, we demonstrated that SCF treatment may help to improve intestinal dynamics by regulating the number and function of ICCs.

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Abbreviations

ICC:

Interstitial cells of Cajal

SMC:

Smooth muscle cells

SCF:

Stem cell factor

GI:

Gastrointestinal

SID:

Stomach–intestine dyskinesis

VIP:

Vasoactive intestinal peptide

CX43:

Connexin 43

NOS1:

NO synthase-1

NKA:

Na+-K+-ATPase

ENS:

Enteric nervous system

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Acknowledgments

We thank Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin 150081, China.

Funding

This work was supported by the National Natural Science Fund (No. 81372611), the National Natural Science Youth Fund (No. 81301750) and the key project of Heilongjiang Province Educational Administration (No. 12521z017).

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    Authors and Affiliations

    1. Department of Gynecology, Third Affiliated Hospital, Harbin Medical University, Harbin, People’s Republic of China

      Dan Kong, Bairong Xia & Ge Lou

    2. Department of Pathology, Basic Medical Science College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150081, People’s Republic of China

      Jing Li, Lei Zhang, Yan He, Lei Gao & Xiaoming Jin

    3. Department of Pathology, Basic Medical Science College, Harbin Medical University, Daqing, People’s Republic of China

      Baoshan Zhao & Xiuli Wang

    4. Department of Orthopedics, Second Clinical Hospital, Harbin Medical University, Harbin, People’s Republic of China

      Yufu Wang

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    1. Dan Kong
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    Correspondence to Xiaoming Jin or Ge Lou.

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    Dan Kong and Jing Li contributed equally to this work.

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    Kong, D., Li, J., Zhao, B. et al. The effect of SCF and ouabain on small intestinal motility dysfunction induced by gastric cancer peritoneal metastasis. Clin Exp Metastasis 32, 267–277 (2015). https://doi.org/10.1007/s10585-015-9702-9

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    • DOI: https://doi.org/10.1007/s10585-015-9702-9

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