Fibroblast growth factor-binding protein 1 (FGFBP1) promotes fibroblast growth factor (FGF) activity by releasing FGFs from extracellular matrix storage. We previously reported that the tumor suppressor F-box and WD repeat domain-containing 7 suppresses FGFBP1 by reducing expression of c-Myc, which inhibits the proliferation and migration of pancreatic cancer cells. However, the potential mechanism by which FGFBP1 facilitates pancreatic ductal adenocarcinoma (PDAC) remains unexplored. In this study, we focused on the function of FGFBP1 in the interplay between cancer-associated fibroblasts (CAFs) and pancreatic cancer cells (PCCs). Decreased FGF22 expression was detected in CAFs co-cultured with PCCs with FGFBP1 abrogation, which was verified in the cell culture medium by enzyme-linked immunosorbent assay. Active cytokine FGF22 significantly facilitated the migration and invasion of PANC-1 and Mia PaCa-2 cells. The number of penetrating PCCs cocultured with CAFs with FGF22 abrogation was significantly less than that of the control group. Interestingly, higher expressions of FGF22 and fibroblast growth factor receptor 2 (FGFR2) were associated with worse prognosis of patients with PDAC and FGFR2, an independent prognostic marker of PDAC. The PANC-1 and Mia PaCa-2 cells with silenced FGFR2 showed weaker invasion and metastasis, even if these cells were simultaneously treated with cytokine FGF22. These results revealed that FGFBP1-mediated interaction between CAFs and PCCs via FGF22/FGFR2 facilitates the migration and invasion of PCCs. FGFR2 could act as a prognostic marker for patients with PDAC.

中文翻译：

---

FGFBP1介导的成纤维细胞与胰腺癌细胞通过FGF22/FGFR2的串扰促进胰腺癌的侵袭和转移

成纤维细胞生长因子结合蛋白 1 (FGFBP1) 通过从细胞外基质储存中释放 FGF 来促进成纤维细胞生长因子 (FGF) 活性。我们之前报道过肿瘤抑制因子 F-box 和 WD 重复结构域包含 7 通过降低 c-Myc 的表达来抑制 FGFBP1，从而抑制胰腺癌细胞的增殖和迁移。然而，FGFBP1 促进胰腺导管腺癌 (PDAC) 的潜在机制仍未探索。在这项研究中，我们关注 FGFBP1 在癌症相关成纤维细胞 (CAF) 和胰腺癌细胞 (PCC) 之间相互作用中的功能。在与 FGFBP1 消除的 PCC 共培养的 CAF 中检测到 FGF22 表达降低，这在细胞培养基中通过酶联免疫吸附测定进行了验证。活性细胞因子 FGF22 显着促进 PANC-1 和 Mia PaCa-2 细胞的迁移和侵袭。与 FGF22 缺失的 CAF 共培养的穿透性 PCC 的数量显着少于对照组。有趣的是，FGF22 和成纤维细胞生长因子受体 2 (FGFR2) 的较高表达与 PDAC 和 FGFR2（PDAC 的独立预后标志物）患者的较差预后相关。具有沉默 FGFR2 的 PANC-1 和 Mia PaCa-2 细胞显示出较弱的侵袭和转移，即使这些细胞同时用细胞因子 FGF22 处理。这些结果表明，FGFBP1 介导的 CAFs 和 PCCs 之间通过 FGF22/FGFR2 的相互作用促进了 PCCs 的迁移和侵袭。FGFR2 可以作为 PDAC 患者的预后标志物。