PTX3 Modulates Neovascularization and Immune Inflammatory Infiltrate in a Murine Model of Fibrosarcoma.

Abstract

Fibrosarcoma is an aggressive subtype of soft tissue sarcoma categorized in infantile/congenital-type and adult-type. Fibrosarcoma cells and its surrounding immune inflammatory infiltrates overexpress or induce the expression of fibroblast growth factor-2 (FGF-2) that have a crucial role in tumor progression and angiogenesis. The inflammation-associated long pentraxin 3 (PTX3) was found to reduce FGF-2-mediated angiogenesis, but its role on fibrosarcoma immune inflammatory infiltrate is still unknown. In this study, we have evaluated the PTX3 activity on immune infiltrating mast cells, macrophages and T-lymphocytes by immunohistochemistry on murine MC-TGS17-51 fibrosarcoma cells and on transgenic TgN(Tie2-hPTX3) mouse. In these fibrosarcoma models we found a reduced neovascularization and a significant decrease of inflammatory infiltrate. Indeed, we show that PTX3 reduces the level of complement 3 (C3) deposition reducing fibrosarcoma progression. In conclusion, we hypothesize that targeting fibrosarcoma microenvironment by FGF/FGFR inhibitors may improve treatment outcome.

• Authors: Tiziana Annese, Roberto Ronca, Roberto Tamma, Arianna Giacomini, Simona Ruggieri, Elisabetta Grillo, Marco Presta, Domenico Ribatti
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 18 (Sep 17 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31533326 (Publication Type: Journal Article)

Chemical References

• Serum Amyloid P-Component
• PTX3 protein
• C-Reactive Protein

Topics

• Animals
• C-Reactive Protein (genetics, metabolism)
• Cell Line, Tumor
• Disease Models, Animal
• Fibrosarcoma (etiology, metabolism, pathology)
• Gene Expression
• Immunohistochemistry
• Immunomodulation
• Inflammation (complications, genetics, immunology, metabolism)
• Male
• Mice
• Neovascularization, Pathologic (genetics, metabolism)
• Serum Amyloid P-Component (genetics, metabolism)
• Tumor Microenvironment (genetics, immunology)