Characterization of neuropeptide-receptor cross-talk driving metastatic liver colonization by disseminated cancer cells (B12)

• Subject Area: Hematology, Oncology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429280966

Liver organotropism is a hallmark of cancer. According to the "seed and soil" theory of metastasis, molecular cross-talk between cancer cells and non-tumorous parenchyma-derived cells underlies liver colonization. Our previous work and unpublished data reveal strong chemotactic effects of liver- and sympathetic-nerve-derived neuropeptide Y (Npy) on disseminated cancer cells that express Npy-receptors. The Npy/Npy-receptor cross-talk could drives homing, nerve infiltration and liver colonization by disseminated cancer cells. In this project, we aim at characterizing this molecular cross-talk between the liver metastatic niche and disseminated cancer cells applying in vitro and in vivo model systems as well as analyzing patient samples. Moreover, the Npy-dependent transcriptome in metastatic cells and its influence on EMT-induced gene signatures will be characterized. Furthermore, evaluation of potential therapeutic targetability of newly revealed pathways driving Npy-mediated metastasis will be addressed.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 305: Striking a moving target: From mechanisms of metastatic colonization to novel systemic therapies
• Applicant Institution: Universität Regensburg
• Project Heads: Professorin Dr. Anja-Katrin Bosserhoff; Dr. Peter Dietrich, Ph.D.