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Title :Crucial role of carbonic anhydrase IX in tumorigenicity of xenotransplanted adult T-cell leukemia-derived cells
Authors :Nasu, Kentaro
Yamaguchi, Kazunori
Takanashi, Tomoka
Tamai, Keiichi
Sato, Ikuro
Ine, Shoji
Sasaki, Osamu
Satoh, Kennichi
Tanaka, Nobuyuki
Tanaka, Yuetsu
Fukushima, Takuya
Harigae, Hideo
Sugamura, Kazuo
Issue Date :Mar-2017
Abstract :Carbonic anhydrase IX (CA9) is a membrane-associated carbonic anhydrase that regulates cellular pH, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA9 in the tumorigenicity of cells derived from human adult T-cell leukemia/lymphoma (ATL). We previously established the highly tumorigenic ST1-N6 subline from the ATL-derived ST1 cell line by serial xenotransplantation in NOG mice. In the present study, we first show that CA9 expression is strongly enhanced in ST1-N6 cells. We then sorted ST1 cells by high or low CA9 expression and established ST1-CA9(high) and ST1-CA9(low) sublines. ST1-CA9(high) cells, like ST1-N6 cells, were more strongly tumorigenic than ST1-CA9(low) or parental ST1 cells when injected into NOG mice. Knockdown of CA9 with shRNAs suppressed the ability of ST1-CA9(high) cells to initiate tumors, and the tumorigenicity of ST1 cells was significantly enhanced by introducing wild-type CA9 or a CA9 mutant with deletion of an intracytoplasmic domain. However, a CA9 with point mutations in the catalytic site did not increase the tumorigenicity of ST1 cells. Furthermore, we detected a small population of CA9(+)CD25(+) cells in lymph nodes of ATL patients. These findings suggest that CA9, and particularly its carbonic anhydrase activity, promotes the tumorigenicity of ATL-derived cells and may be involved in malignant development of lymphoma-type ATL.
URL :https://doi.org/10.1111/cas.13163
Type Local :雑誌掲載論文
ISSN :1349-7006
Publisher :Wiley
URI :http://hdl.handle.net/20.500.12000/45871
Citation :Cancer science Vol.108 no.3 p.435 -443
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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