DEFICIENCY OF THE SOLUBLE PATTERN RECOGNITION RECEPTOR PENTRAXIN-3 INCREASES SUSCEPTIBILITY TO TUMOR GROWTH AND METASTASIS

The long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor involved in innate immunity, inflammation, tissue remodelling and female fertility. Moreover PTX3 binds fibroblast growth factor-2 (FGF-2) and inhibits its angiogenic activity. PTX3 is elevated in several pathological conditions reflecting in particular the involvement of the vascular bed as ischemic heart disease, atherosclerosis, small vessel vasculitis and preeclampsia. PTX3 plasma levels are elevated in cancer patients, such as in soft tissue liposarcoma and chondrosarcoma. As PTX3 is a structural component of the cumulus oophorus extracellular matrix in human and mouse, through the interaction with hyaluronic acid binding proteins TNF- α -stimulated gene-6 (TSG-6) and inter-α-trypsin inhibitor (IαI), we hypothesized that PTX3 could be a component of other extracellular matrices such as in the tumor stroma. Moreover, being produced by tumor stromal cells (endothelial cells, fibroblasts, leukocytes), PTX3 could play a role in modulating inflammation associated with tumor growth. To address the involvement of PTX3 in tumor growth, we used a model of non immunogenic and metastatic murine fibrosarcoma (MN/MCA1) and we observed an increased tumor growth and metastatic potential associated with PTX3 deficiency. Moreover in a model of immunogenic fibrosarcoma (MCA203) we observed an accelerated tumor growth in PTX3 knock out mice compared to wild type mice. Mechanisms potentially involved in the mentioned phenotypes range from regulation of angiogenesis and inflammation to organization of the extracellular matrix (ECM) through the direct interaction with ECM components and are currently under investigation. The preliminary results obtained in this study suggest that PTX3 could be a potential therapeutic target in tumor growth.