Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA177

Poster Communications

Hypoxia related pathways in the pathomechanism of bladder cancer

N. Koll1, Y. Schild1, L. Lober1, J. Fandrey1

1. Institute for Physiology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.

Bladder cancer (BC) ranges among the tenth most cancers worldwide. Two main forms of BC exist, superficial (sBC) and muscle invasive BC (miBC). Different therapies are in use but the treatment success is not always convincing. For different treatment opportunities every second patient with miBC died within the next five years after diagnosis and up to 40% of patients with sBC get relapses after standard therapy like Bacillus-Calmette-Guarin (BCG)-instillation. The decision for the right therapy is challenging because prediction of therapy success is difficult. (1) This is why there is necessity of new prognostic markers for a successful treatment and better understanding of the pathomechanism of BC. Hypoxia often occurs in big solid tumors, likewise in BC, and it seems to play a role in progression and metastatic spread of BC. Hypoxia is also one hallmark of inflammation. Repeated inflammation is suspected to favor the development of BC. But the immune system seems to play a paradox role in the pathomechanism of BC. For example BCG-instillation induces a massive immune-response which prevents the recurrence of sBC. But repeated infections of the urinary tract seem to promote BC while the frequent use of NSAID (non-steroid anti-inflammatory drugs) seems to be protective. (1) The aim of the study is to discover new coherences between hypoxia related pathways and growth behavior including metastatic potential of BC cells (BCCs) and interaction of BCCs with immune cells. Therefore different human cell lines were used: superficial (RT4) and transitional (J82) BCCs, one immortalized normal urothelial cell line, and immune cells. The present data characterize J82 and RT4 cells under normoxia (21% O2) and hypoxia (1% O2) for proliferation and migration, hypoxia inducible factors (HIFs)- and target gene-mRNA expression and HIF-protein stabilization. Hypoxia inducible factors are the main regulatory transcription factors for the adaptation of mammalian cells to hypoxia. HIFs and their target genes are used as parameters for cellular reaction to hypoxia. All used cell lines react to hypoxia by stabilizing HIF-1α protein and increased expression of HIF-1α target genes. Interestingly proliferation and migration are not affected by hypoxia. Studies are underway with co-culture of BCCs (monolayer or spheroids) with different immune cell types under varying conditions (hypoxia and HIF-1α knock down or inhibition) to better understand the behavior of BCCs in interaction with immune cells with special focus on hypoxia related pathways.

Where applicable, experiments conform with Society ethical requirements