Crucial role of carbonic anhydrase IX in tumorigenicity of xenotransplanted adult T-cell leukemia-derived cells
Bibliographic Information
- Other Title
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- Crucial role of carbonic anhydrase IX in tumorigenicity of xenotransplanted adult T‐cell leukemia‐derived cells
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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.
論文
Journal
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- Cancer science
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Cancer science 108 (3), 435-443, 2017-03
Wiley
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Details 詳細情報について
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- CRID
- 1050574201770888064
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- NII Article ID
- 120006844097
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- ISSN
- 13497006
- 13479032
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- HANDLE
- 20.500.12000/45871
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN