Open AccessM2‐like macrophage polarization in high lactic acid‐producing head and neck cancer
Author(s) -
Ohashi Toshimitsu,
Aoki Mitsuhiro,
Tomita Hiroyuki,
Akazawa Takashi,
Sato Katsuya,
Kuze Bunya,
Mizuta Keisuke,
Hara Akira,
Nagaoka Hitoshi,
Inoue Norimitsu,
Ito Yatsuji
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13244
Subject(s) - lactic acid , macrophage polarization , head and neck squamous cell carcinoma , warburg effect , macrophage , cancer research , m2 macrophage , chemistry , biology , in vitro , metabolism , head and neck cancer , biochemistry , cancer , glycolysis , bacteria , genetics
Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a pro‐inflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of LDHA and GLUT 1 , which are related to the Warburg effect, in human head and neck squamous cell carcinoma ( HNSCC ). Tumors expressing lower levels of LDHA and GLUT 1 had a higher concentration of lactic acid than those with higher LDHA and GLUT 1 expression. Lactic acid also suppressed the expression of LDHA and GLUT 1 in vitro . We previously reported that lactic acid enhances expression of an M2 macrophage marker, ARG 1 , in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, CSF 1R and CD 163 , normalized using a pan‐macrophage marker, CD 68 . Tumors with lower levels of CD 68 showed a higher concentration of lactic acid, whereas those with higher levels of CSF 1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD 163 . These results suggest that tumor‐secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2‐like macrophage polarization in human HNSCC .