Cluster of Excellence –
University of Freiburg

Microenvironment remodeling by the degradome of breast cancer stem cells

PD Dr. Thomas Reinheckel, Prof. Dr. Christoph Peters, Dr. Oliver Schilling (Institute of Molecular Medicine and Cell Research)

Carcinomas contain cell populations with stem cell properties that are critical for tumor growth, tumor spread, and colonization of distant sites. Proteolysis is a hallmark feature of invasive growth and metastasis – thus we aim to functionally characterize the degradome, i.e. the complement of proteases and their endogenous protease inhibitors, of cancer stem cells in its ability to remodel the microenvironment of those cells. To this end, the processing of ECM proteins by surface-bound or secreted proteases of stem cells and the functional implication of these cleavage events will be studied in stem cell culture and in vivo by orthotopic transplantation of cancer stem cells with genetic or pharmacologic perturbation of the protease network.

Figure: Colonies grown from primary sorted breast cancer stem cells are proteolytically active. A) 3D-colonies embedded in a matrix of fluorescence quenched collagen. B) Proteolytic cleavage results in dequenching of the fluorescence signal (green). C) Propidium iodine staining for dead cells (red). D) Overlay of A, B, and C