Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment

Annan, Dorcas A.; Maishi, Nako; Soga, Tomoyoshi; Dawood, Randa; Li, Cong; Kikuchi, Hiroshi; Hojo, Takayuki; Morimoto, Masahiro; Kitamura, Tetsuya; Alam, Mohammad Towfik; Minowa, Kazuyuki; Shinohara, Nobuo; Nam, Jin-Min; Hida, Yasuhiro; Hida, Kyoko

Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment

Annan, Dorcas A.; Maishi, Nako; Soga, Tomoyoshi et al.

Cell communication and signaling, 2019, 17(1), 169

Permalink : https://hdl.handle.net/2115/77025

このアイテムのアクセス数:646件（2026-08-08 08:11 集計）

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https://doi.org/10.1186/s12964-019-0478-4			18

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アクセス権	open access
URI	https://hdl.handle.net/2115/77025
タイトル	Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment
著者	Annan, Dorcas A. ; Maishi, Nako ; Soga, Tomoyoshi ; Dawood, Randa ; Li, Cong ; Kikuchi, Hiroshi ; Hojo, Takayuki ; Morimoto, Masahiro ; Kitamura, Tetsuya ; Alam, Mohammad Towfik ; Minowa, Kazuyuki ; Shinohara, Nobuo ; Nam, Jin-Min ; Hida, Yasuhiro ; Hida, Kyoko
e-Rad_Researcher 30837240 著者名 Annan, Dorcas A.
e-Rad_Researcher 00632423 著者名 Maishi, Nako
著者名 Soga, Tomoyoshi
著者名 Dawood, Randa
著者名 Li, Cong
著者名 Kikuchi, Hiroshi
e-Rad_Researcher 60756691 著者名 Hojo, Takayuki
著者名 Morimoto, Masahiro
e-Rad_Researcher 00451451 著者名 Kitamura, Tetsuya
e-Rad_Researcher 60641694 著者名 Alam, Mohammad Towfik
e-Rad_Researcher 30209845 著者名 Minowa, Kazuyuki
e-Rad_Researcher 90250422 著者名 Shinohara, Nobuo
e-Rad_Researcher 60414132 著者名 Nam, Jin-Min
e-Rad_Researcher 30399919 著者名 Hida, Yasuhiro
e-Rad_Researcher 40399952 著者名 Hida, Kyoko
言語	英語
キーワード	Lactic acidosis
	Tumor endothelial cells
	Carbonic anhydrase 2 (CAII)
	pH regulation
	Angiogenesis
発行日	2019-12-17
出版者	BioMed Central
収録物名	Cell communication and signaling
巻(号)	17(1)
ページ	169
抄録	Background Tumor endothelial cells (TECs) perform tumor angiogenesis, which is essential for tumor growth and metastasis. Tumor cells produce large amounts of lactic acid from glycolysis; however, the mechanism underlying the survival of TECs to enable tumor angiogenesis under high lactic acid conditions in tumors remains poorly understood. Methodology The metabolomes of TECs and normal endothelial cells (NECs) were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The expressions of pH regulators in TECs and NECs were determined by quantitative reverse transcription-PCR. Cell proliferation was measured by the MTS assay. Western blotting and ELISA were used to validate monocarboxylate transporter 1 and carbonic anhydrase 2 (CAII) protein expression within the cells, respectively. Human tumor xenograft models were used to access the effect of CA inhibition on tumor angiogenesis. Immunohistochemical staining was used to observe CAII expression, quantify tumor microvasculature, microvessel pericyte coverage, and hypoxia. Results The present study shows that, unlike NECs, TECs proliferate in lactic acidic. TECs showed an upregulated CAII expression both in vitro and in vivo. CAII knockdown decreased TEC survival under lactic acidosis and nutrient-replete conditions. Vascular endothelial growth factor A and vascular endothelial growth factor receptor signaling induced CAII expression in NECs. CAII inhibition with acetazolamide minimally reduced tumor angiogenesis in vivo. However, matured blood vessel number increased after acetazolamide treatment, similar to bevacizumab treatment. Additionally, acetazolamide-treated mice showed decreased lung metastasis. Conclusion These findings suggest that due to their effect on blood vessel maturity, pH regulators like CAII are promising targets of antiangiogenic therapy.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	1478-811X
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1186/s12964-019-0478-4