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

Jing Li,Lei Gao,Xiaoming Jin,Duanyang Liu,Yan He,Xiuli Wang,Yufu Wang,Meisi Yan,Jiade Li,Dan Kong,Lei Zhang

doi:10.1111/jcmm.12575

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.

Highlights

Malignant ascites is a common complication that occurs at the late stage of malignant cancers and is associated with the characteristics of persistent, massive and recurrent tumours, which seriously threaten the quality of life of patients
Malignant ascites changes the environment of the abdominal cavity, and the tumour microenvironment (TME), which exerts a profound influence on the functions of specific organs, tissues and cells [1, 2]
Lymphocytes in the ascites are known as tumour-infiltrating lymphocytes (TILs), which are mainly composed of CD3+ T cells, CD8+ T cells and CD4+ T cells [7,8,9]

Summary

Introduction

Malignant ascites is a common complication that occurs at the late stage of malignant cancers and is associated with the characteristics of persistent, massive and recurrent tumours, which seriously threaten the quality of life of patients. Malignant ascites changes the environment of the abdominal cavity, and the tumour microenvironment (TME), which exerts a profound influence on the functions of specific organs, tissues and cells [1, 2]. Interstitial cells of Cajal (ICCs) are mesoderm-derived mesenchymal cells that contribute to normal gastrointestinal motility. Interstitial cells of Cajal generate pacemaker potentials that drive the electrical slow waves that contribute to normal neuromuscular signalling. Some factors in the TME could polarize macrophages towards the tumour-associated macrophages (TAMs) phenotype. Tumour-infiltrating lymphocytes and TAMs are the important messengers between the inflammatory microenvironment of the tumour and the tumour cells, as they promote angiogenesis, lymphangiogenesis and matrix remodelling.

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