Epirubicin suppresses proliferative and metastatic potential by downregulating transforming growth factor‐β‐induced expression in urothelial carcinoma

Abstract

Transforming growth factor‐β‐induced (TGFΒI) is considered to be a vital gene in several carcinomas. In this study we determined the effect of TGFBI on the proliferative and metastatic potential of human urothelial carcinoma (UC) cells as well as its mRNA and protein expression, which were detected by RT‐PCR and western blot, respectively. UC cell proliferation was analyzed by WST‐1 assay and Hoechst 33258 staining. The effect of TGFBI on UC cell metastasis was analyzed using adhesion, migration and invasion assays. We found that TGFBI increased the proliferation of UC cells. Moreover, TGFBI enhanced the adhesion, migration and invasion of UC cells by upregulating MMP‐2, MMP‐9 and calpain‐2 expression. We evaluated the effect of Epirubicin (EPI) on the regulation of TGFBI expression and found that TGFBI acts as a downstream target of EPI and is suppressed by EPI in UC cells. EPI is more effective in inhibiting the proliferation and metastasis of UC cells with high TGFBI expression. This study demonstrates that TGFBI might lead to tumorigenesis and progression of UC and those cells with high TGFBI expression may be vulnerable to relapse. EPI could prove to be a therapeutic option in patients with high TGFBI expressing UC cells.

TGFBI Protein Is Increased in the Urine of Patients with High-Grade Urothelial Carcinomas, and Promotes Cell Proliferation and Migration

“…In line with these observations, we showed a tumor promoting function of TGFBI in bladder cancer in vitro, in terms of enhanced cell proliferation and migration. Our results are further supported by a study from Shang and colleagues, who demonstrated in RT112 and 253J bladder cancer cell lines [40], that siRNA-mediated low TGFBI expression significantly decreased proliferation, adhesion, migration and invasion. In contrast, overexpression of TGFBI in these bladder cancer cells significantly enhanced all those cellular functions.…”

<p>Collagen stiffness promoted non-muscle-invasive bladder cancer progression to muscle-invasive bladder cancer</p>

“…Binding of collagen to integrin is mediated by TGFBI 35. In addition, TGFBI can activate matrix metalloproteinase (MMP) secretion and promote invasion 36. We found that silencing COL1A1 down-regulated the expression levels of TGFBI and MMP9.…”

Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix

“…These include TGF‐β signaling [ 37 ]. TGFβI is an ECM protein functionally linked to fibronectin [ 38 ], as it serves as a linker protein that mediates integrin binding to extracellular proteins, such as fibronectin, collagen, and laminins [ 39 ]. Epithelial OC cells have the potential to switch between epithelial and mesenchymal states during metastasis, and previous findings showed that the TGFβI signaling significantly impacts epithelial‐to‐mesenchymal transition and promotes the malignant potential of OC spheroid cells [ 38 ].…”