In their recent article on biomarker-based risk of pancreatic cancer,1 the authors analyse the potential value of Trefoil protein 1 (TFF1) as a component of a PancRISK panel. Our group has been long involved in studying pancreatic cancer.2,3 This paper particularly attracted our attention, because some members of our group have previous experience in the study of TFF1.4,5 In particular, we showed that copper binding, promoting the TFF1 homodimerisation, increased its motogenic activity in in vitro wound-healing assays.4 That finding appeared to suggest a possible activity of TFF1 on cancer cell motility.
In the same period of the publication of the article by Blyuss et al.,1 another article reported the anticancer activity of some copper complexes in pancreatic cancer cells.6 Due to the role of copper in TFF1 activity, we might speculate that the anticancer effect of copper complexes in pancreatic cancer can be due to a possible interference of the complexes with the correct TFF1–copper interaction.
We believe that these different pieces of evidence concur in supporting a role for TFF1 in pancreatic cancer, and that this topic can be worthy of further studies.
Blyuss, O., Zaikin, A., Cherepanova, V., Munblit, D., Kiseleva, E. M., Prytomanova, O. M. et al. Development of PancRISK, a urine biomarker-based risk score for stratified screening of pancreatic cancer patients. Br. J. Cancer 122, 692–696 (2020).
Rosati, A., Basile, A., D’Auria, R., d’Avenia, M., De Marco, M., Marzullo, L. et al. BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages. Nat. Commun. 6, 8695 (2015).
Iorio, V., Rosati, A., D’Auria, R., De Marco, M., Marzullo, L., Basile, A. et al. Combined effect of anti-BAG3 and anti-PD-1 treatment on macrophage infiltrate, CD8+ T cell number and tumour growth in pancreatic cancer. Gut 67, 780–782 (2018).
Tosco, A., Monti, M. C., Fontanella, B., Montefusco, S., D’Andrea, L., Ziaco, B. et al. Copper binds the carboxy-terminus of trefoil protein 1 (TFF1), favoring its homodimerization and motogenic activity. Cell Mol. Life Sci. 67, 1943–1955 (2010).
Montefusco, S., Esposito, R., D’Andrea, L., Monti, M. C., Dunne, C., Dolan, B. et al. Copper promotes TFF1-mediated Helicobacter pylori colonization. PLoS ONE 8, e79455 (2013).
Carcelli, M., Tegoni, M., Bartoli, J., Marzano, C., Pelosi, G., Salvalaio, M. et al. In vitro and in vivo anticancer activity of tridentate thiosemicarbazone copper complexes: unravelling an unexplored pharmacological target. Eur. J. Med. Chem. 194, 112266 (2020).
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De Marco, M., Rosati, A., Turco, M.C. et al. Comment on: ‘Development of PancRISK, a urine biomarker-based risk score for stratified screening of pancreatic cancer patients’. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-1013-5