Project Details
Projekt
Investigations into the influence of pretubulysin and archazolid on endothelial processes responsible for tumor cell adhesion and transmigration
Applicant
Professor Dr. Robert Fürst
Subject Area
Pharmacology
Term
from 2010 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 159663715
Metastasis, i.e. the formation of a secondary tumor at a distant place via the hematogenic or lymphogenic way of dissemination, is the main cause for death in cancer patients. Thus, the development and characterization of anti-metastatic agents is a major task in cancer research. This research group has shown that the myxobacterial compounds archazolid and pretubulysin, besides direct effects on tumor cells and the tumor vasculature (endothelial cells), can prevent cancer cell dissemination. This project aims to characterize the action of the two compounds on endothelial cells responsible for the inhibition of cancer cell extravasation, a key step in metastasis, and to analyze the mechanisms involved. We have found that archazolid and pretubulysin induce the adhesion of tumor cells (MDA-MB-231 breast cancer cells) to the endothelium, inhibit their transmigration (diapedesis), and affect the CXCL12/CXCR4 system. Thus, we will focus on the involvement of (i) cell adhesion molecules and (ii) the mentioned chemokine system and will elucidate the underlying signaling pathways. Also leukocytes will be taken into account, since they can facilitate extravasation events. Moreover, further aims are to characterize the anti-angiogenic potential of soraphen A and to test novel pretubulysin and chondramide derivatives for their effects on important endothelial functions (endothelial cell-tumor cell and endothelial cell-leukocyte interaction, angiogenesis).
DFG Programme
Research Units
