Disseminated cancer cell-derived extracellular vesicles in early metastatic organ colonisation (B09)

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

Melanoma spread to lymph nodes of the regional basin is a major predictor for melanoma outcome. Since lymph nodes are often resected, they offer the unique opportunity to catch human disseminated melanoma cells (DCCs) before and during metastatic colony formation and to study their interplay with local immune cells. Transcriptome analysis of DCCs identified activation of DCC-derived extracellular vesicle (EVs) production during colony formation, which was paralleled by CD8 T cell exhaustion, strongly suggesting a fundamental role of EVs in DCC-niche communication. We hypothesize that metastatic colony formation is driven by DCC-derived EVs, which modulate phenotype and function of surrounding immune cells and provide growth support to yet pre-colonizing DCC-clones and whose production is activated by oncogenic pathways. The goal of the project is to identify and mechanistically dissect the role of molecular constituents of DCC-derived EVs and oncogenic pathways involved therein.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 305: Striking a moving target: From mechanisms of metastatic colonization to novel systemic therapies
• Major Instrumentation: Zeta View Win
• Instrumentation Group: 1950 Partikelzählgeräte und -klassiergeräte (optisch, elektronisch, außer 35
• Applicant Institution: Universität Regensburg
• Project Head: Privatdozentin Dr. Melanie Werner-Klein