Ronca Roberto, Tamma Roberto, Coltrini Daniela, Ruggieri Simona, Presta Marco, Ribatti Domenico
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
Oncotarget. 2017 Aug 1;8(47):82583-82592. doi: 10.18632/oncotarget.19773. eCollection 2017 Oct 10.
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 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.
肥大细胞是前列腺肿瘤微环境的重要调节因子。成纤维细胞生长因子/成纤维细胞生长因子受体（FGF/FGFR）系统在前列腺肿瘤的生长、血管生成和进展中发挥着非冗余的自分泌/旁分泌作用。因此，FGF拮抗剂长五聚体蛋白3（PTX3）和源自PTX3的小分子FGF陷阱NSC12已被证明可抑制包括前列腺癌在内的不同FGF依赖性肿瘤类型的生长和血管生成。在本研究中，我们表明重组FGF2在基质胶栓试验中能够引起肥大细胞募集。相反，转基因小鼠中PTX3的过表达或用FGF抑制剂NSC12处理会导致TRAMP-C2肿瘤移植瘤（一种前列腺癌小鼠模型）的生长和血管生成受到显著抑制，同时肥大细胞浸润到病变中的数量也相应减少。这些数据证实并扩展了先前关于肥大细胞对FGF2刺激产生趋化反应能力的观察结果，并为人类前列腺腺癌中肥大细胞募集、血管生成和肿瘤生长之间的关系提供了证据。
