IL-34 and CSF-1 promote the survival and proliferation of monocytes, as well as their differentiation into macrophages via the CSF-1R. Both cytokines can polarize macrophages into immunosuppressive M2 macrophages. In cancer, IL-34 is produced by several types of tumor cells and contributes to therapy resistance and disease progression. In addition to CSF-1R, receptor-type protein-tyrosine phosphatase zeta (PTPRZ1) was also identified as IL-34 receptor and shown to be at play, suggesting that IL-34 also exerts specific functions independently of the CSF-1R. Activation of PTPRZ1 leads to increased tyrosine phosphorylation of several signaling pathways and is upregulated in many human cancers, regulating cancer cell migration and metastasis. We are studying the physiological and pathological roles and the underlying molecular mechanisms of IL-34 and its receptors CSF-1R and PTPRZ1 in cancer.
Angiopoietin-like 4 (ANGPTL4), best known for its role as an adipokine involved in the regulation of lipid and glucose metabolism, has recently been ascribed a critical role in cancer growth and progression. We are evaluating the mechanisms of ANGPTL4 on neovascularization, tumor growth and metastasis aiming to characterize ANGPTL4 at the molecular and functional level in a range of in vitro assays and small animal models. Furthermore, we are analyzing the effect of ANGPTL4-mediated tumor-stromal interactions on promotion of invasive cancer cell growth and establishment of a specific hypoxic microenvironment to unravel its effect on the behavior of malignant cancer cells.
During heart failure, increased numbers of immune cells and transformed cardiac fibroblasts make excess extracellular matrix (ECM) resulting in pathological fibrosis. In collaboration with the Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research at the Medical University of Vienna we investigate the role of ECM remodeling and reverse remodeling in heart failure using preclinical models of cardiac remodeling.