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S100A4 and S100A6 Proteins Expression Promote Migration of Bladder Cancer Cells in Zebrafish

Author: Hanaa Al‑Mahmoodi, Ibtihal Alshamarti1, Qais Ibraheem Al‑Ismaeel2, Ahmed Mohamed Salih3, Hishyar Azo Najeeb4, Rusul Mohammed Al‑Rubaay5
Journal: Medical Journal of Babylon مجلة بابل الطبية ISSN: 1812156X 23126760 Year: 2019 Volume: 16 Issue: 3 Pages: 192-198
Publisher: Babylon University جامعة بابل


Background: Bladder cancer (BC) is one of the major causes of cancer‑related mortality in the world. S100 family of small Ca‑bindingproteins has been implicated in the progression of different cancer types, including BC. Objective: The goal of this study is to develop a morerigorous understanding of the role of S100 proteins in BC progression and also to what extent S100s have the ability to increase the metastaticpotential for BC. Methods: A selected panel of bladder cell lines (J82, T24, HT1376, and RT112) was transplanted into zebrafish embryosto investigate their migration behavior and metastatic potential. Characterizing the expression pattern of S100 proteins including (S100A4and S100A6) in different BC cells was performed using quantitative polymerase chain reaction and Western blot. Assess the effect of S100proteins on bladder cell migration in vivo was carried out using a zebrafish xenotransplant model. S100 proteins expression was modulated bysmall‑interfering RNA approach. Results: High expression of mRNA and proteins levels of S100A4 and A6 were detected in T24 and J82 celllines, which displayed the highest migration rate in zebrafish embryos. In addition, our data showed that the average migration rate of T24 cellstransfected against S100A4, S100A6, and S100A4 and A6 were 17.3%, 10%, and 17.3%, respectively, which was lower than from siControl41.9%. Likewise, the same effect of protein silencing on cell migration was observed in J82 cell lines. S100A4, S100A6, and S100A4 andA6 knockdown reduced the migration rate of J82 cells to 14.6%, 17%, and 14% compared to the control 37.8%. Furthermore, overexpressedS100A4 expression in RT112 cells significantly increased in migration ability by 29%, compared to control cells 7.3%. Conclusion: S100A4and S100A6 play a role in BC cells invasion and migration. Silencing of these proteins affected dissemination of BC cells in zebrafish embryoshighlighting their role in tumor progression.

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