Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA178

Poster Communications

Characterizations of human pancreatic tumor cell lines under normoxic and hypoxic conditions

A. Wrobeln1, V. Bäcker1, T. Günther1, J. Sydow1, J. Fandrey1

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

With a median survival rate of about 5 %, over a period of 5 years after diagnosis, pancreatic cancer is one of the most abrasive cancer types (1). Until today curative therapy is still missing. To develop a successful treatment deeper understanding of the cellular processes involved in pancreatic tumor development and growth is indispensable. Since hypoxia has an important role in tumor development (2), we investigated hypoxia inducible factors (HIF) in human pancreatic cancer cell lines (hPCCs). Because even less is known about the interaction between pancreatic tumor cells and infiltrating immune cells under hypoxic conditions we started experiments under conditions of inflammatory hypoxia. i.e. a process of combined hypoxia and immune cell activation, and identified suitable pancreatic tumor cell lines for detailed investigation of HIF and the connected pathways. Four different hPCCs (HPAC, PSN-1, KP-4, HuP-T4) were used. Expression of mRNA and protein levels as well as proliferation and migration under normoxic (20% O2) and hypoxic (1% O2) conditions were analyzed. Comparison of the different hPCCs under the applied conditions showed similar behavior with varying extent. The hypoxic status of the hPCCs was verified by qPCR analysis of HIF1α mRNA expression and immunoblot of stabilized HIF1α protein. Under hypoxia hPCCs revealed increasing HIF1α mRNA levels and stabilized HIF1α protein compared to control cells under normoxia. Furthermore, tumor cell proliferation was decreased compared to that under normoxic conditions. In almost the same manner hPCCs displayed a better migration under normoxia compared to hypoxia. The present data demonstrate that the investigated hPCCs (HPAC, PSN-1, KP-4, HuP-T4) are influenced by hypoxia. In conclusion, these first results indicate that the characterized hPCCs are useful for further observations with regard to cellular processes which are associated to pancreatic tumor development and growth. Further experiments will investigate interaction of hPCCs with different immune cells under normoxic and hypoxic conditions, to get a deeper understanding of the cellular events involved in the pancreatic tumor development and growth.

Where applicable, experiments conform with Society ethical requirements