Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer

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ABSTRACT

A solid tumor consists of cancer and stromal cells, which comprise the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are usually abundant in the TME, contributing to tumor progression. In cases of peritoneal dissemination of gastric cancer (GC), the contribution of intraperitoneal TAMs remains unclear. Macrophages from peritoneal washings of GC patients were analyzed, and the link between intraperitoneal TAMs and GC cells was investigated to clarify the interaction between them in peritoneal dissemination. Macrophages were predominant among leukocytes constituting the microenvironment of the peritoneal cavity. The proportion of CD163-positive TAMs was significantly higher in stage IV than in stage I GC. Co-culture with TAMs potentiated migration and invasion of GC. IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination. An elevated concentration of intraperitoneal IL-6 was correlated with a poor prognosis in clinical cases. In conclusion, intraperitoneal TAMs are involved in promoting peritoneal dissemination of GC via secreted IL-6. TAM-derived IL-6 could be a potential therapeutic target for peritoneal dissemination of GC.

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Most cited references 33

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Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.

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Macrophages in Tumor Microenvironments and the Progression of Tumors

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Establishment and characterization of a human acute monocytic leukemia cell line (THP-1).

M Yamabe, K Tada, Y. Yamaguchi … (1980)

A human leukemic cell line (THP-1) cultured from the blood of a boy with acute monocytic leukemia is described. This cell line had Fc and C3b receptors, but no surface or cytoplasmic immunoglobulins. HLA haplotypes of THP-1 were HLA-A2, -A9, -B5, -DRW1 and -DRW2. The monocytic nature of the cell line was characterized by: (1) the presence of alpha-naphthyl butyrate esterase activities which could be inhibited by NaF; (2) lysozyme production; (3) the phagocytosis of latex particles and sensitized sheep erythrocytes; and (4) the ability to restore T-lymphocyte response to Con A. The cells did not possess Epstein-Barr virus-associated nuclear antigen. These results indicate that THP-1 is a leukemia cell line with distinct monocytic markers. During culture, THP-1 maintained these monocytic characteristics for over 14 months.

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Author and article information

Journal

Journal ID (nlm-ta): Oncoimmunology

Journal ID (iso-abbrev): Oncoimmunology

Journal ID (publisher-id): KONI

Journal ID (publisher-id): koni20

Title: Oncoimmunology

Publisher: Taylor & Francis

ISSN (Print): 2162-4011

ISSN (Electronic): 2162-402X

Publication date Collection: 2019

Publication date (Electronic): 22 October 2019

Publication date PMC-release: 22 October 2019

Volume: 8

Issue: 12

Electronic Location Identifier: e1671760

Affiliations

[a ]Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama, Japan

[b ]Minimally Invasive Therapy Center, Okayama University Hospital , Okayama, Japan

[c ]Center for Innovative Clinical Medicine, Okayama University Hospital , Okayama, Japan

Author notes

CONTACT Shunsuke Kagawa skagawa@ 123456md.okayama-u.ac.jp Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , 2-5-1 Shikata-cho, Kita-ku, Okayama 700–8558, Japan

Author information

Shunsuke Kagawa http://orcid.org/0000-0002-3610-8211

Kazuya Kuwada http://orcid.org/0000-0001-5923-6913

Tetsuya Kagawa http://orcid.org/0000-0001-6820-3830

Ryuichi Yoshida http://orcid.org/0000-0003-3017-7088

Satoru Kikuchi http://orcid.org/0000-0002-7671-0696

Shinji Kuroda http://orcid.org/0000-0002-4484-1253

Hiroshi Tazawa http://orcid.org/0000-0003-4658-1050

Toshiyoshi Fujiwara http://orcid.org/0000-0002-5377-6051

Article

Publisher ID: 1671760

DOI: 10.1080/2162402X.2019.1671760

PMC ID: 6844331

PubMed ID: 31741772

SO-VID: 7d26d2a4-e563-4a5b-9bbf-be57619d231d

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 14 June 2019

Date revision received : 12 September 2019

Date accepted : 18 September 2019

Page count

Figures: 6, References: 63, Pages: 14

Funding

Funded by: Japan Society for the Promotion of Science 10.13039/501100001691

Award ID: JP15K15193

Award ID: JP16H05416 JP18K08679

Funded by: Ministry of Health, Labor and Welfare 10.13039/501100003478

Award ID: 14525167

This work was supported by Japan Society for the Promotion of Science [KAKENHI Grant Numbers JP15K15193, JP16H05416 JP18K08679], and Ministry of Health, Labor and Welfare [14525167].

Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer

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HLA-G and immune tolerance in pregnancy

Most cited references 33

Global cancer statistics, 2012.

Macrophages in Tumor Microenvironments and the Progression of Tumors

Establishment and characterization of a human acute monocytic leukemia cell line (THP-1).

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