S100A4 and S100A6 proteins expression promote migration of bladder cancer cells in Zebrafish

Abstract EN

Background: Bladder cancer (BC) is one of the major causes of cancer‑related mortality in the world.

S100 family of small Ca‑binding proteins has been implicated in the progression of different cancer types, including BC.

Objective: The goal of this study is to develop a more rigorous understanding of the role of S100 proteins in BC progression and also to what extent S100s have the ability to increase the metastatic potential for BC.

Methods: A selected panel of bladder cell lines (J82, T24, HT1376, and RT112) was transplanted into zebrafish embryos to investigate their migration behavior and metastatic potential.

Characterizing the expression pattern of S100 proteins including (S100A4 and S100A6) in different BC cells was performed using quantitative polymerase chain reaction and Western blot.

Assess the effect of S100 proteins on bladder cell migration in vivo was carried out using a zebrafish xenotransplant model.

S100 proteins expression was modulated by small‑interfering RNA approach.

Results: High expression of mRNA and proteins levels of S100A4 and A6 were detected in T24 and J82 cell lines, which displayed the highest migration rate in zebrafish embryos.

In addition, our data showed that the average migration rate of T24 cells transfected against S100A4, S100A6, and S100A4 and A6 were 17.3%, 10%, and 17.3%, respectively, which was lower than from siControl 41.9%.

Likewise, the same effect of protein silencing on cell migration was observed in J82 cell lines.

S100A4, S100A6, and S100A4 and A6 knockdown reduced the migration rate of J82 cells to 14.6%, 17%, and 14% compared to the control 37.8%.

Furthermore, overexpressed S100A4 expression in RT112 cells significantly increased in migration ability by 29%, compared to control cells 7.3%.

Conclusion: S100A4 and S100A6 play a role in BC cells invasion and migration.

Silencing of these proteins affected dissemination of BC cells in zebrafish embryos highlighting their role in tumor progression.