Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer

Background: No curative therapy is currently available for metastatic prostate cancer (PCa). The diverse mechanisms of progression include fibroblast growth factor (FGF) axis activation. Objective: To investigate the molecular and clinical implications of fibroblast growth factor receptor 1 (FGFR1) and its isoforms (alpha/beta) in the pathogenesis of PCa bone metastases. Design, setting, and participants: In silico, in vitro, and in vivo preclinical approaches were used. RNA-sequencing and immunohistochemical (IHC) studies in human samples were conducted. Outcome measurements and statistical analysis: In mice, bone metastases (chi-square/Fisher's test) and survival (Mantel-Cox) were assessed. In human samples, FGFR1 and ladinin 1 (LAD1) analysis associated with PCa progression were evaluated (IHC studies, Fisher's test). Results and limitations: FGFR1 isoform expression varied among PCa subtypes. Intracardiac injection of mice with FGFR1-expressing PC3 cells reduced mouse survival (alpha, p < 0.0001; b, p = 0.032) and increased the incidence of bone metastases (alpha, p < 0.0001; beta, p = 0.02). Accordingly, IHC studies of human castration-resistant PCa (CRPC) bone metastases revealed significant enrichment of FGFR1 expression compared with treatment-naive, nonmetastatic primary tumors (p = 0.0007). Expression of anchoring filament protein LAD1 increased in FGFR1-expressing PC3 cells and was enriched in human CRPC bone metastases (p = 0.005). Conclusions: FGFR1 expression induces bone metastases experimentally and is significantly enriched in human CRPC bone metastases, supporting its prometastatic effect in PCa. LAD1 expression, found in the prometastatic PCa cells expressing FGFR1, was also

Automated summary

This study found that FGFR1 expression plays an important role in bone metastasis of prostate cancer, and its activity enhanced bone metastasis and survival rate in mice, and the human samples also showed that FGFR1 were enriched in bone metastasis of castration-resistant prostate cancer. In addition, the study also found that the LAD1 protein co-expressed with FGFR1 plays an important role in the bone metastasis of prostate cancer.