Abstract
Mast cells are important modifiers of prostate tumor microenvironment. The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) system plays a non-redundant autocrine/paracrine role in the growth, vascularization and progression of prostate tumors. Accordingly, the FGF antagonist long pentraxin-3 (PTX3) and the PTX3-derived small molecule FGF-trap NSC12 have been shown to inhibit the growth and vascularization of different FGF-dependent tumor types, including prostate cancer. In this study, we show that recombinant FGF2 is able to cause mast cell recruitment in vivo in the Matrigel plug assay. Conversely, PTX3 overexpression in transgenic mice or treatment with the FGF inhibitor NSC12 result in a significant inhibition of the growth and vascularization of TRAMP-C2 tumor grafts, a murine model of prostate cancer, that were paralleled by a decrease of mast cell infiltrate into the lesion. These data confirm and extend previous observations about the capacity of mast cells to respond chemotactically to FGF2 stimulation and provide evidence about a relationship among mast cell recruitment, angiogenesis, and tumor growth in human prostate adenocarcinoma.
Highlights
A tight cross-talk exists between inflammation and cancer, tumor-infiltrating inflammatory cells producing various cytokines that regulate the inflammatory response in the tumor-bearing host
PTX3 overexpression in transgenic mice or treatment with the fibroblast growth factor (FGF) inhibitor NSC12 result in a significant inhibition of the growth and vascularization of TRAMP-C2 tumor grafts, a murine model of prostate cancer, that were paralleled by a decrease of mast cell infiltrate into the lesion
The capacity of FGF2 to induce an angiogenic response and mast cell recruitment was investigated in vivo by quantitative PCR analysis applied to a murine Matrigel plug assay [31]
Summary
A tight cross-talk exists between inflammation and cancer, tumor-infiltrating inflammatory cells producing various cytokines that regulate the inflammatory response in the tumor-bearing host. Mast cells express a variety of growth factors/ angiogenic mediators and their accumulation correlates with increased neovascularization, tumor aggressiveness and poor prognosis in different solid and hematologic tumors [1]. A correlation has been established between mast cell density and microvessel density in human prostate adenocarcinoma [3]. Tryptase-positive mast cells are present in both intratumoral and peritumoral areas of prostate adenocarcinoma with an overlapping mean density [4]. Mast cell number in the intratumoral and peritumoral regions of prostate adenocarcinoma is significantly higher as compared to benign lesions [5]. Mast cells promote welldifferentiated adenocarcinoma growth in human patients and in the autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model [6]
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