Osteopontin accelerates the development and metastasis of bladder cancer via activating JAK1/STAT1 pathway

Abstract

Background: Bladder cancer is the 10th common cancer worldwide. Osteopontin has been found to enhance cell proliferation, metastasis and invasion in various human tumors.

Objective: To investigate the roles of osteopontin in bladder cancer.

Methods: The RNA interference and overexpression of osteopontin were performed in bladder cancer cell lines (T24 and SCaBER). Cell proliferation and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. Cell invasion was determined using transwell assay.

Results: Osteopontin was highly expressed in bladder cancer tissues in comparison with the adjacent normal tissues. Its high expression significantly correlated with high histologic grade, high TNM stage (III and IV) and poor prognosis. For T24 cells with osteopontin interference and SCaBER cells with osteopontin overexpression, cell proliferation was significantly inhibited (3.58-fold vs. 5.62-fold) and enhanced (7.81-fold vs. 5.29-fold), respectively. The apoptosis portion of T24 cells significantly increased from 4.48 to 10.75%, and that of SCaBER cells significantly declined from 7.33 to 4.01%. The invaded T24 and SCaBER cells significantly decreased to 52.0% and increased to 2.0-fold, respectively. Osteopontin overexpression enhanced the expression (1.54-fold and 2.39-fold; 2.33-fold and 2.05-fold) and activation (1.80-fold and 1.96-fold; 2.00-fold and 2.59-fold) of JAK1 and STAT1 in two cell lines of bladder cancer.

Conclusion: Osteopontin might enhance proliferation, inhibit apoptosis and accelerate invasion and thus promote the development and metastasis of bladder cancer, and osteopontin's functions might be mediated by activating JAK1/STAT1 signaling pathway.

Keywords: Bladder cancer; Invasion; JAK1/STAT1 pathway; Osteopontin; Proliferation.