PROSTATE CANCER

FGF2 causes genomic instability

Previously unaddressed questions concerning the role of fibroblast growth factor 2 (FGF2) in prostate cancer have been investigated in new research. The results of this study show that exogenous FGF2 causes chromosomal imbalances and DNA breakages in prostate cancer cells. Stromal FGF2 expression was positively associated with unfavourable clinicopathological features. Treatments targeting the tumour stroma could have promise for patients with prostate cancer.

In vitro, treatment with recombinant FGF2 (rFGF2) increased the number of abnormal centrosomes and DNA-damage-associated foci in LNCAP and PC3 cells. Aberrant mitoses were also increased in these cells. In LNCAP cells, rFGF2 treatment caused increased numbers of chromosome 8. Co-treatment of LNCAP cells with rFGF plus the FGF receptor inhibitor dovitinib reduced the number of cells with abnormal centrosomes, chromosome 8 numbers, and DNA damage.

In vivo, bone-forming patient-derived xenografts (PDXs) with high endogenous FGF2 expression and hyperactivation of the FGF signalling axis exhibited increased mitosis and aberrant mitoses. These PDXs also had increased numbers of DNA-damage-associated foci.

In patient samples, immunohistochemical analysis showed that strong stromal FGF2 staining was associated with increased Gleason grade, pT stage, lymph node metastases, distant metastases, and biochemical recurrence.

Overall, these data show that FGF2 induces genomic instability in prostate cancer cells and that increased stromal FGF2 expression is associated with adverse clinicopathological features in patients with prostate cancer. Understanding the biological basis of these findings could lead to new treatments for this disease.

References

Original article

  1. Pecqueux, C. et al. FGF-2 is a driving force for chromosomal instability and a stromal factor associated with adverse clinico-pathological features in prostate cancer. Urol. Oncol. https://doi.org/10.1016/j.urolonc.2018.05.020 (2018)

    PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Louise Stone.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Stone, L. FGF2 causes genomic instability. Nat Rev Urol 15, 528 (2018). https://doi.org/10.1038/s41585-018-0058-1

Download citation

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing