Project Details
Projekt
Molecular Characterization of Bone Metastasis Founder Cells in Prostate Cancer
Applicants
Miodrag Guzvic, Ph.D.; Professor Dr. Christoph Klein
Subject Area
Hematology, Oncology
Pathology
Pathology
Term
from 2018 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 401324861
Disseminated prostate cancer cells (DCCs) in bone marrow (BM) comprise the founder cells of later arising lethal bone metastases and understanding the biology of BM-DCCs is paramount for an improved clinical management of prostate cancer (PC) patients. We found that DCCs in prostate cancer displayed significant genetic heterogeneity. Notably, preliminary analysis of the transcriptome indicates that DCCs in PC express a mixed epithelial/haematopoietic phenotype, suggesting a complex patter of adaptation to the ectopic BM microenvironment. We have collected genomes and transcriptomes from almost 400 PC BM-DCCs. In this project we will use novel single cell sequencing technologies to characterize genomes and transcriptomes of BM-DCCs. Furthermore, we will correlate the molecular data with the clinical outcome, and in particular look for (i) genetic aberrations and mutations enabling metastatic progression, and (ii) pathways responsible for quiescence or proliferation of DCCs. For this part of the project, we will collaborate with the team of Ana Dubrovska, and exchange the molecular data obtained from DCCs and circulating tumor cells specific for different stages of the disease. In collaboration with the team of Gelinsky/Alblas we will use their in vitro culture system for BM to model the biology of DCC. We will use prostate cancer and patient-derived metastatic cell lines to establish conditions for expansion of early metastasis founder cells. The resulting in vitro model of minimal residual prostate cancer will enable us to perform further functional assays and drug screens aiming to eradicate the lethal seed of metastasis before clinical manifestation.
DFG Programme
Priority Programmes
