Browsing by Subject "carbonic anhydrase 9"

Hepatoblastoma (HB) is the most common malignant pediatric liver tumor. Although developed treatments have increased the survival rate of HB patients, 20-30 % of the patients show lack of response to the currently used treatment. Due to rapid growth and insufficient blood flow, solid tumors, like HB, develop areas with low oxygen levels. This condition is called tumor hypoxia. Tumor hypoxia correlates with poor prognosis, higher metastasis rate and resistance to cancer treatments. In response to hypoxia, cancer cells start to express carbonic anhydrase 9 (CA9) via HIF1. CA9 contributes to the maintenance of alkaline intracellular pH. That promotes tumor development, while the increasingly acidic extracellular space promotes tumor cell invasiveness. CA9 has historically been related to carcinogenic processes in a variety of cancers, and it has been hypothesized that it may be a possible target for cancer therapy. Substances for the inhibition of CA9 already exist, and one of them, SLC-0111, has given promising results in phase I clinical trials as well as several pre-clinical studies. The aim of this study is to describe the expression of CA9 in HB and study their relationship to pathological features in cellular level, especially the viability and migration of cancer cells. Another purpose of the study is to investigate the effect of SLC-0111 on HB cells and to consider its significance as a potential treatment. CA9 is expressed in two different HB cell lines, HUH6 and HB-303-LEF when exposed to hypoxic conditions. Cells show more aggressive behavior under hypoxic conditions. HB-303-LEF migrates more abruptly in hypoxia compared to normoxic cells. Cells from both cell lines in spheroid modeling, in which CA9 was inhibited by SLC-0111, showed lower viability. HB-303-LEF also showed slower migration in hypoxia where it had received the SLC-0111 inhibitor compared to hypoxic cells. HUH6 results were parallel but not statistically significant. Cells behave more aggressively in hypoxia. The use of SLC-0111 contributes to the reduction of viability and migration. It can be considered an interesting discovery for future treatments against HB.