Role of CTSK-MMP-9 Crosstalk in Epithelial Tumor Progression

Prof. Dr. Prasad Shastri (BIOSS and Institute of Macromolecular Chemistry, University of Freiburg)

Cancer remains the leading cause of death in the developed world second only to cardiovascular diseases. While the overall 5-year survival rate in women where the cancer is localized or regionalized (limited to draining lymph node) is >99% and 85%, respectively, this survival rate dramatically falls to < 26% when the tumor has metastasized to distal organs. It has been shown that epithelial cells that metastasize express cathepsin-K (Cat-K), an endopeptidase, commonly expressed by osteoclasts and synovial fibroblasts. We have discovered that the Cat-K can activate pro-MMP-9, a master regulator of tumor development; therefore the Cat-K phenotype might represent a very critical step in the evolution of a tumor cell. Understanding how acquisition of Cat-K expression in breast tumor cells can improve our insights to factors that promote breast cancer metastasis. We are combining near-infrared functional molecular tomography with a multicellular a spheroid model derived from human tumor epithelial cells, human endothelial cells and human marrow-derived mesenchymal stem cells (MSCs) - the Synthetic Tumor Microenvironment mimics (STEMs) – to get a more accurate description of how changes in primary tumor proteomics influence migratory capacity of breast tumor epithelial cells and bone metastasis.