CA IX and Inflammatory Cytokines in Pancreatic Cancer – a functional cross-talk

Authors: Sabína Strapcová 1    Oľga Sedláková 1    Lubomíra Lukačíková 1    Mária Bartošová 1    Lucia Csáderová 1    Jozef Bizík 2    Božena Smolková 2    Eliška Švastová 1   
1 Biomedicínske centrum SAV, Oddelenie nádorovej biológie, Bratislava    2 Biomedicínske centrum SAV, Oddelenie molekulárnej onkológie, Bratislava   
Year: 2020
Section: Cellular metabolism, physiology, molecular biology and genetics
Abstract No.: 1968
ISBN: 978-80-972360-6-9

Carbonic anhydrase IX (CA IX), a transmembrane zinc metalloenzyme, is expressed in a variety of solid tumours via the HIF pathway. Through its involvement in the pH regulating apparatus and the metastatic cascade, CA IX drives the formation of an acidic tumor microenvironment, mediates cell survival, migration and metastatic lesion formation. Thus, CA IX serves as a marker of bad prognosis, a diagnostic marker, and a promising therapeutic target in different carcinomas. While CA IX is poorly expressed in the healthy pancreas, CA IX expression in pancreatic cancer favors malignant progression and correlates with poor patient survival. Since CA IX expression in vivo was shown to be controlled via additional hypoxia-unrelated mechanisms of the tumor micorenvironment, and pancreatitis remains the leading risk factor for PDAC development, we explore the functional cross-talk between CA IX and inflammatory molecules. In pancreatic cancer lines, we show that inflammatory cytokines up-regulate CA9 transcription even in normoxia and that inflammatory cytokines promote the aggressive tumour phenotype by up‑regulating mesenchymal markers, cell-stemmnes markers, and ECM‑degrading metalloproteinases. We assume that CA IX plays a principal role in this type of malignancy, particularly in combination with inflammation, by proving that protein inhibition in vitro negatively affects cancer cell migration and adhesion on collagen I – a matrix excessively overexpressed in pancreatic cancer patients.

Acknowledgement: This work was supported by APVV 14-0816, VEGA 2/0105/19, VEGA 2/0052/18 and by the H2020 project VISION grant agreement No 857381.