Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres, 98166 Messina, Italy.
IOM Ricerca Srl, Via Penninazzo 11, 95029 Viagrande, Italy.
Cells. 2023 Mar 24;12(7):1002. doi: 10.3390/cells12071002.
Cancer is the leading cause of death worldwide; thus, it is necessary to find successful strategies. Several growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), and transforming growth factor beta (TGF-β), are involved in the main processes that fuel tumor growth, i.e., cell proliferation, angiogenesis, and metastasis, by activating important signaling pathways, including PLC-γ/PI3/Ca signaling, leading to PKC activation. Here, we focused on bFGF, which, when secreted by tumor cells, mediates several signal transductions and plays an influential role in tumor cells and in the development of chemoresistance. The biological mechanism of bFGF is shown by its interaction with its four receptor subtypes: fibroblast growth factor receptor (FGFR) 1, FGFR2, FGFR3, and FGFR4. The bFGF-FGFR interaction stimulates tumor cell proliferation and invasion, resulting in an upregulation of pro-inflammatory and anti-apoptotic tumor cell proteins. Considering the involvement of the bFGF/FGFR axis in oncogenesis, preclinical and clinical studies have been conducted to develop new therapeutic strategies, alone and/or in combination, aimed at intervening on the bFGF/FGFR axis. Therefore, this review aimed to comprehensively examine the biological mechanisms underlying bFGF in the tumor microenvironment, the different anticancer therapies currently available that target the FGFRs, and the prognostic value of bFGF.
癌症是全球主要的死亡原因;因此,有必要寻找成功的策略。几种生长因子,如血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF、FGF2)和转化生长因子-β(TGF-β),通过激活重要的信号通路,如 PLC-γ/PI3/Ca 信号通路,导致 PKC 激活,参与了促进肿瘤生长的主要过程,即细胞增殖、血管生成和转移。在这里,我们重点关注 bFGF,当它由肿瘤细胞分泌时,介导几种信号转导,并在肿瘤细胞和化疗耐药性的发展中发挥重要作用。bFGF 的生物学机制与其四个受体亚型:成纤维细胞生长因子受体(FGFR)1、FGFR2、FGFR3 和 FGFR4 的相互作用有关。bFGF-FGFR 的相互作用刺激肿瘤细胞增殖和侵袭,导致促炎和抗凋亡肿瘤细胞蛋白的上调。考虑到 bFGF/FGFR 轴在肿瘤发生中的参与,已经进行了临床前和临床研究,以开发新的治疗策略,单独或联合使用,旨在干预 bFGF/FGFR 轴。因此,本综述旨在全面研究 bFGF 在肿瘤微环境中的生物学机制、目前针对 FGFRs 的不同抗癌疗法以及 bFGF 的预后价值。