Carbonic-anhydrase IX expression is increased in thyroid cancer tissue and represents a potential therapeutic target to eradicate thyroid tumor-initiating cells. (15th September 2021)

• Record Type: Journal Article
• Authors: Schmidt, Jennifer; Oppermann, Elsie; Blaheta, Roman A.; Schreckenbach, Teresa; Lunger, Ilaria; Rieger, Michael A.; Bechstein, Wolf Otto; Holzer, Katharina; Malkomes, Patrizia
• Is Part Of: Molecular and cellular endocrinology. Volume 535(2021)
• Publication Date: 2021-09-15
• Subjects: Carbonic-anhydrase IX -- Thyroid cancer -- Hypoxia -- Tumor-initiating cells -- Methazolamide; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2021.111382
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The expression of Carbonic-anhydrase IX (CAIX) in thyroid cancer (TC) subtypes was determined and its role in cancer cell growth and tumor-initiating cells (TICs) investigated. Immunohistochemistry in 114 TC patients revealed that CAIX expression was increased in tumor specimens of papillary, follicular and anaplastic TCs compared to normal thyroid tissue. Clinicopathological data indicated that lymph node metastases were more frequent in patients with high CAIX expression. The Cancer Genome Atlas database analysis demonstrated that a strong CAIX-mRNA expression was associated with advanced tumor stages and poor survival in TCs. In TC cell lines, CAIX expression was elevated in tumorspheres compared to monolayer cultures and was associated with an increased expression of stemness markers. Genetic knockdown or pharmacological inhibition of CAIX suppressed cell proliferation and the TIC ability to form tumorspheres by an induction of apoptosis and cell-cycle arrest. These findings suggest CAIX as a potential prognostic marker and a therapeutic target for thyroid cancer. Graphical abstract: Image 1 Highlights: CAIX expression is increased in thyroid cancer. High CAIX expression correlates with advanced tumor stages and poor overall survival. CAIX is upregulated in thyrospheres and correlated with expression of stemness markers. Knockdown of CAIX suppresses thyroid cancer cell proliferation and TIC activity. CAIX inhibition exerts anti-tumor effect by inducing apoptosis and cell-cycle arrest.