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      The impact of inflammatory cells in malignant ascites on small intestinal ICCs’ morphology and function

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          Abstract

          Malignant ascites is one of the common complication at the late stage of abdominal cancers, which may deteriorate the environment of abdominal cavity and lead to potential damage of functional cells. Interstitial cells of Cajal (ICCs) are mesoderm-derived mesenchymal cells that function normal gastrointestinal motility. The pathological changes of ICCs or the reduced number may lead to the motility disorders of gastrointestinal tract. In this study, through analysis of malignant ascites which were obtained from cancer patients, we found that inflammatory cells, including tumour-infiltrating lymphocytes, accounted for 17.26 ± 1.31% and tumour-associated macrophages, occupied 19.06 ± 2.27% of total cells in the ascites, suggesting these inflammatory cells, in addition to tumour cells, may exert important influence on the tumour environment of abdominal cavity. We further demonstrated that the number of mice ICCs were significant decreased, as well as morphological and functional damage when ICCs were in the simulated tumour microenvironment in vitro. Additionally, we illustrated intestinal myoelectrical activity reduced and irregular with morphological changes of ICCs using the mice model of malignant ascites. In conclusion, our data suggested that inflammatory cells in malignant ascites may damage ICCs of the small intestine and lead to intestinal motility disorders.

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          Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis.

          The presence of T cells within the epithelial component of tumors, as histologic evidence of anti-tumor immunity, has been associated with a survival advantage in multiple studies across diverse patient cohorts. We performed a meta-analysis of studies evaluating the prognostic value of tumor-infiltrating lymphocytes (TIL) on survival among women with ovarian cancer and to investigate factors associated with variations in this effect, including patient characteristics, surgical outcomes, tumor histology, and study protocols. Published studies that evaluated the association between TIL and patient survival were identified. Descriptive statistics, outcome data, and study quality were extracted from studies that met inclusion criteria. Hazard ratios and 95% confidence intervals were pooled across studies using the random-effects model. Publication bias was investigated using a funnel plot and heterogeneity was assessed with subgroup analysis and I(2) statistics. Ten suitable studies comprising 1815 patients with ovarian cancer were analyzed. Our results demonstrate that a lack of intraepithelial TILs is significantly associated with a worse survival among patients (pooled HR: 2.24, 95% CI; 1.71-2.91). Variations in the prognostic value of TIL status based on debulking status, scoring method, and geographic regions were identified. Intraepithelial TILs are a robust predictor of outcome in ovarian cancer and define a specific class of patients, whose distinct tumor biology should be taken into account in devising appropriate therapeutic strategies. Copyright © 2011 Elsevier Inc. All rights reserved.
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            The Tumor Microenvironment Contribution to Development, Growth, Invasion and Metastasis of Head and Neck Squamous Cell Carcinomas

            Head and neck squamous cell carcinoma (HNSCC) is a complex tissue that contains tumor cells and the surrounding stroma, which is populated by different types of mesenchymal cells and the extracellular matrix (ECM). Collectively, they are referred to as the tumor microenvironment (TME). Recent studies have shown that TME has a more profound influence on the growth and metastasis of HNSCC than was previously appreciated. Because carcinoma-associated fibroblasts (CAFs) are frequently observed in the stroma of the tumor, this review focuses on the potential role of tumor-CAFs interactions in progression of HNSCC. Tumor-CAFs crosstalk enhances the production of growth factors, cytokines, chemokines, matrix metalloproteinases (MMPs), and inflammatory mediators, which eventually facilitates tumor growth. In fact, factors and cells that do not support tumor growth are usually down regulated or mitigated in TME. Therefore TME may determine the fate of the tumors at the site of invasion and metastasis. For tumor cells that survive at these sites, stromal activation may serve to establish a supportive tumor stroma, fostering the outgrowth of the metastatic cells. The concept of tumor-stromal interactions and microenvironmental niche has profound consequences in tumor growth and metastasis and therefore, it's understanding will open up new strategies for the diagnosis, prognosis and therapy of HNSCC.
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              Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract.

              Populations of interstitial cells of Cajal (ICC) are altered in several gastrointestinal neuromuscular disorders. ICC are identified typically by ultrastructure and expression of Kit (CD117), a protein that is also expressed on mast cells. No other molecular marker currently exists to independently identify ICC. The expression of ANO1 (DOG1, TMEM16A), a Ca(2+)-activated Cl(-) channel, in gastrointestinal stromal tumors suggests it may be useful as an ICC marker. The aims of this study were therefore to determine the distribution of Ano1 immunoreactivity compared with Kit and to establish whether Ano1 is a reliable marker for human and mouse ICC. Expression of Ano1 in human and mouse stomach, small intestine, and colon was investigated by immunofluorescence labeling using antibodies to Ano1 alone and in combination with antibodies to Kit. Colocalization of immunoreactivity was demonstrated by epifluorescence and confocal microscopy. In the muscularis propria, Ano1 immunoreactivity was restricted to cells with the morphology and distribution of ICC. All Ano1-positive cells in the muscularis propria were also Kit positive. Kit-expressing mast cells were not Ano1 positive. Some non-ICC in the mucosa and submucosa of human tissues were Ano1 positive but Kit negative. A few (3.2%) Ano1-positive cells in the human gastric muscularis propria were labeled weakly for Kit. Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells.
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                Author and article information

                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                jcmm
                Journal of Cellular and Molecular Medicine
                John Wiley & Sons, Ltd (Chichester, UK )
                1582-1838
                1582-4934
                September 2015
                18 June 2015
                : 19
                : 9
                : 2118-2127
                Affiliations
                [a ]Department of Pathology, Basic Medical Science College, Harbin Medical University Harbin, China
                [b ]Department of Gynecology, Third Affiliated Hospital of Harbin Medical University Harbin, China
                [c ]Department of Pathology, Basic Medical Science College, Harbin Medical University Daqing, China
                [d ]Department of Orthopedics, Second Clinical Hospital, Harbin Medical University Harbin, China
                Author notes
                * Correspondence to: Xiaoming JIN,, Department of Pathology, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, China., Tel./fax: 0086-451-86669472, E-mail: jinxm55@ 123456163.com
                [#]

                Jing Li and Dan Kong contributed equally to this work.

                Article
                10.1111/jcmm.12575
                4568916
                26087333
                4b55f1c7-f181-4a9a-b6b9-262675f054fc
                © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 October 2014
                : 05 February 2015
                Categories
                Original Articles

                Molecular medicine
                malignant ascites,interstitial cell of cajal,inflammatory cells,tumour microenvironment,tumour-infiltrating lymphocyte,tumour-associated macrophage

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