FGFBP1-mediated crosstalk between fibroblasts and pancreatic cancer cells via FGF22/FGFR2 promotes invasion and metastasis of pancreatic cancer

Abstract

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 CAF cocultured 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.

Identifying a baicalein-related prognostic signature contributes to prognosis prediction and tumor microenvironment of pancreatic cancer

“…It was proposed that FGFBP1 could enhance the functions of fibroblast growth factor by releasing FGFs from the extracellular matrix (39). cocultured with PDAC cells with FGFBP1 abrogation suggesting role of FGFBP1 in FGF-mediated CAF regulation (40). In the study, we employed high-throughput RNA sequencing for novel target screening of baicalein.…”

Requirement of CLIC4 Expression in Human Colorectal Cancer Cells for Sensitivity to Growth Inhibition by Fucoxanthinol

“…IFIT1 is an interferonstimulated inflammation-related protein that promotes cell invasion, metastasis, and tumor development (51). FGFBP1 releases fibroblast growth factors-interacting fibroblast growth factor receptors from extracellular matrix and enhances the migration and invasion of cancer cells (52). SLC1A3 is a glutamate/aspartate transporter that promotes spreading, and integrin signals in human cervical cancer (HeLa) and breast cancer (MDA-MB-231) cells, while enhancing their cell motility (16).…”

Exploring the Structural and Functional Diversity among FGF Signals: A Comparative Study of Human, Mouse, and Xenopus FGF Ligands in Embryonic Development and Cancer Pathogenesis

“…Furthermore, FGF21 is vital in preventing the onset of advanced diseases, such as pancreatic ductal adenocarcinoma or hepatocellular carcinoma (Table 3), by delaying the onset of the fatty pancreas, steatopancreatitis, fatty liver, and steatohepatitis [167]. Additionally, FGF22 aids pancreatic cancer cell invasion and migration [168]. Hence, developing analogs of FGF21 and antagonists of FGF22 could be therapeutically beneficial for treating chronic liver and pancreas diseases.…”