TY - JOUR
T1 - Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer
AU - Sakamoto, Shuichi
AU - Kagawa, Shunsuke
AU - Kuwada, Kazuya
AU - Ito, Atene
AU - Kajioka, Hiroki
AU - Kakiuchi, Yoshihiko
AU - Watanabe, Megumi
AU - Kagawa, Tetsuya
AU - Yoshida, Ryuichi
AU - Kikuchi, Satoru
AU - Kuroda, Shinji
AU - Tazawa, Hiroshi
AU - Fujiwara, Toshiyoshi
N1 - Funding Information:
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]. The authors would like to thank Tomoko Sueishi, Yuko Hoshijima, Noriko Imagawa, and Tae Yamanishi for excellent technical support.
Publisher Copyright:
© 2019, © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2019/12/2
Y1 - 2019/12/2
N2 - 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.
AB - 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.
KW - Gastric cancer
KW - peritoneal dissemination
KW - tumor microenvironment
KW - tumor-associated macrophages
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U2 - 10.1080/2162402X.2019.1671760
DO - 10.1080/2162402X.2019.1671760
M3 - Article
C2 - 31741772
AN - SCOPUS:85074558465
VL - 8
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 12
M1 - e1671760
ER -
