Project Details
Projekt
The role of tumor-associated macrophages in bone metastasis formation in zebrafish
Applicant
Professorin Dr. Franziska Knopf
Subject Area
Hematology, Oncology
Developmental Biology
Cell Biology
Developmental Biology
Cell Biology
Term
from 2018 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 401262365
The aim of this project is to better understand cancer cell colonisation into bone and to unravel unknown interactions between tumour, immune and bone cells in the bone niche. To elucidate such interactions, in vivo imaging of transplanted breast cancer cells in larval zebrafish will be used. In general, in vivo imaging is a powerful tool in order to demonstrate interplay of cells, also in cancer research. In mice, intravital imaging of tumors has revealed that there is a physical connection of tumor-associated macrophages (TAM) with cancer cells, both during initial invasion of tissues and intravasation of cancer cells, i.e. their entry into the blood stream. During these stages mutual dependence by way of positive feedback loops between cancer cells and TAM has been shown. However, the role of TAM for the cancer cells' exit from the blood stream (extravasation), as well as during colonisation of bone is less well understood. By monitoring the interaction of tumor cells (breast cancer cell lines, CTCs), macrophages and bone cells in living zebrafish bone tissue, the following questions will be addressed: i. How do TAM help cancer cells to extravasate and to initially grow in the bone niche? ii. How do TAM contribute to altered osteoblast and osteoclast function during metastasis? To answer these questions, spinning disc confocal microscopy of transgenic zebrafish, in which the respective cell types are fluorescently labelled, will be used. In these fish, interaction of macrophages with bone and cancer cells can be monitored. This approach will be combined with in vivo bone staining techniques and subsequent bone composition analyses in order to characterize bone lesions at the site of metastasis. Furthermore, changes in macrophage number and function will unravel the molecular links of TAM and cancer cells. Using these tools, the role of TAM in bone metastasis formation will be further elucidated which will help to modulate macrophage function in future anti-cancer therapies.
DFG Programme
Priority Programmes
