Project Details
Projekt
Expression, function and endogenous modulators of transient receptor potential channels TRPV1, TRPV6 and TRPM8 in gastroenteropancreatic neuroendocrine tumors
Subject Area
Gastroenterology
Term
from 2012 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 221906675
Neoplastic properties of neuroendocrine tumors of the gastroenteropancreatic system (GEP-NETs) are, similar to numerous other cancers, determined by calcium-dependent cellular mechanisms. Intracellular calcium is substantially regulated by transient receptor potential channels (TRPs). The functional relevance of the TRP channel subtypes TRPM8, TRPV1, and TRPV6 for the carcinogenesis has been described in various solid tumors. The distinct expression levels of these TRPs in certain solid malignancies (e. g. prostate carcinoma) correlate with the clinical prognosis, and therefore TRPs are considered as novel prognostic markers. In a recent study the applicants demonstrated for the first time that pancreatic NETs express TRPM8. Current investigations revealed overexpression of TRPV1 and decreased expression of TRPV6 in NETs of pancreas and ileum. Given the increased incidence and limited therapeutic options of GEP-NETs, the aim of the project consist of the characterization of the expression and properties of TRPM8, TRPV1 and TRPV6 in regulating tumor biological processes in this malignancy. Using GEP-NET cell models and primary cell cultures, we plan to investigate the molecular, biochemical and pharmacological characteristics of these TRPs and to study their crucial signaling pathways. In addition, we aim to characterize the functional cross-talk between TRPM8, TRPV1 and TRPV6 and the oncogenically-relevant ligands of membrane receptors for IGF-1, EGF and somatostatin in GEP-NETs. Lastly, using in-house established animal models of GEP-NETs, the oncogenic activities of these three different TRPs will be studied. Overall, the results of this study will contribute to a better understanding of the GEP-NETs biology and hold promise to improve and extend of the arsenal of diagnostic and therapeutic tools available to date in this unique neoplastic disease by utilizing TRPs.
DFG Programme
Research Grants
