Chen Liu Qi, Howison Christine M, Spier Catherine, Stopeck Alison T, Malm Scott W, Pagel Mark D, Baker Amanda F
Department of Chemistry and Biochemistry, University of Arizona , Tuscon, AZ , USA.
Leuk Lymphoma. 2015 May;56(5):1432-9. doi: 10.3109/10428194.2014.933218. Epub 2014 Nov 10.
The expression of carbonic anhydrase IX (CA IX) and its relationship to acidosis in lymphomas has not been widely studied. We investigated the protein expression of CA IX in a human B-cell lymphoma tissue microarray, and in Raji, Ramos and Granta 519 lymphoma cell lines and tumor models, while also investigating the relationship with hypoxia. An imaging method, acidoCEST magnetic resonance imaging (MRI), was used to estimate lymphoma xenograft extracellular pH (pHe). Our results showed that clinical lymphoma tissues and cell line models in vitro and in vivo had moderate CA IX expression. Although in vitro studies showed that CA IX expression was induced by hypoxia, in vivo studies did not show this correlation. Untreated lymphoma xenograft tumor pHe had acidic fractions, and an acidity score was qualitatively correlated with CA IX expression. Therefore, CA IX is expressed in B-cell lymphomas and is qualitatively correlated with extracellular acidosis in xenograft tumor models.
碳酸酐酶IX(CA IX)在淋巴瘤中的表达及其与酸中毒的关系尚未得到广泛研究。我们在人B细胞淋巴瘤组织芯片以及Raji、Ramos和Granta 519淋巴瘤细胞系及肿瘤模型中研究了CA IX的蛋白表达,同时也研究了其与缺氧的关系。采用一种成像方法——酸化学交换饱和转移磁共振成像(MRI)来估计淋巴瘤异种移植瘤的细胞外pH值(pHe)。我们的结果显示,临床淋巴瘤组织以及体外和体内的细胞系模型均有中等程度的CA IX表达。虽然体外研究表明CA IX表达由缺氧诱导,但体内研究并未显示这种相关性。未经治疗的淋巴瘤异种移植瘤的pHe有酸性部分,且酸度评分与CA IX表达存在定性相关性。因此,CA IX在B细胞淋巴瘤中表达,且在异种移植瘤模型中与细胞外酸中毒存在定性相关性。