The role of osteopontin in tumor progression

Principal Investigator: Professor Ksenija Lučin

Department: Department of Pathology, Faculty of Medicine

Institution: University of Rijeka, Croatia


Key words: osteopontin, tumor progression, adhesion molecule, tumor microenvironment, prognostic

The progression of the tumor is due to the accumulation of genetic changes and changes in cell function leading to invasion and metastasis of tumors. These changes are regulated by the molecules that act on the signal transduction pathways in the cell, and thus the change in gene expression. One of these molecules is osteopontin (OPN), a protein synthesized by various cell types, including epithelial cells, and secreted into the extracellular space. Acting as a cytokine and as a extracellular matrix protein, OPN binds to cell surface receptors and thus induces signal transmission, regulating numerous physiological and pathological processes. The expression of osteopontin in malignant tumors is increased compared to healthy tissues, suggesting its possible importance in the process of tumor invasion and metastasis. The aim of current study was to investigate the value of osteopontin (OPN) as diagnostic and prognostic marker in the management of patients with some forms of malignant tumors. We have previously shown that OPN plays a role in the progression of kidney, oral cavity, brain and lung cancer, and hematological tumors multiple myeloma and non-Hodgkin's lymphoma. The aim of the following studies is to explore the mechanisms by which OPN mediates its effect: a role in angiogenesis, in the prolonged survival of tumor cells, mediating the immune response, acting together with growth factors, as well as enzymes that degrade the extracellular matrix. Also, we will analyze the receptors by which OPN achieves its effect. Based on the overall findings about the role of OPN in the tumor biology, OPN was recently proposed as a biomarker in clinical work. Moreover, the findings can be used as therapy. The possibilities of blocking action of OPN, including blocking of OPN at the gene level, mRNAs or protein level, and blocking the receptor for OPN, today are intensively studied, which can help to create the so-called "smart" drug for malignant tumors.