ESM-1 silencing decreased cell survival, migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma

Abstract

Endothelial cell-specific molecule-1 (ESM-1) is a secretory proteoglycan comprising a mature polypeptide of 165 amino acids and a single dermatan sulfate. The aim of this study was to evaluate endothelial cell-specific molecule-1 (ESM-1) as a hepatocellular carcinoma (HCC) marker and to analyze the effect of ESM-1 gene silencing in hepatocellular carcinoma cells. RT-PCR and Western Blot analysis revealed overexpression of ESM-1 in human HCC liver tissue and in serum from patients with HCC. Sandwich ELISA assay was used for quantitative analysis of ESM-1 in serum. Levels of ESM-1 were significantly elevated in the serum of patients with HCC (n = 40) as compared to serum from patients with hepatitis (AH, n = 40; CH, n = 39) or liver cirrhosis (n = 40) or from healthy subjects (n = 40). The accuracy of ESM-1 for HCC was higher than that of α-fetoprotein (AFP) according to ROC curve analysis. Expression of ESM-1 siRNA decreased cell survival through the inhibition of NF-κB pathway and induced cell cycle arrest by PTEN induction resulting in the inhibition of cyclin D1 in SK-Hep1 cells. Furthermore, ESM-1 silencing inhibited cell migration and invasion of SK-Hep1 cells. This study demonstrates that ESM-1 as a potential tumor marker is overexpressed in most tissues and serum in the presence of HCC and is involved with cell survival, cell cycle progression, migration, and invasion of hepatocellular carcinoma cells. Based on our results, we suggest that ESM-1 or a combination of ESM-1 and AFP is useful markers for diagnosis of HCC and ESM-1 may be useful therapeutic target of hepatocellular carcinoma.

Serum Proteoglycans as Prognostic Biomarkers of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

“…It also promotes cancer cell survival, migration and invasion in vitro, and tumor growth in vivo, as described in a mouse model of human tumor xenografts (17,18). In humans, the serum level of endocan has been identified as an independent prognostic marker in non-small cell lung cancer (19).…”

Esm1 Modulates Endothelial Tip Cell Behavior and Vascular Permeability by Enhancing VEGF Bioavailability

“…15,16 It is however not known whether this involves alterations in tumor angiogenesis. Esm1 expression in tumors was observed throughout most ECs ( Figure 1B and Online Figure IC), suggesting that it may play a prominent role in tumor angiogenesis.…”

Endocan: A new marker for cancer and a target for cancer therapy

“…The study mutated phenylalanine and subsequently, the HEK 293 cells did not form any tumors despite the presence of the glycan (5). Immunofluorescent staining showed strong ESM-1 expression in the cytoplasm of tumor cells in hepatocellular carcinoma (HCC) tissues when compared to normal tissues (20). A previous study analyzed the tumor tissues and surrounding non-cancerous hepatic parenchyma from 42 primary HCC patients.…”

“…The specificity of ESM-1 was 80.8% and sensitivity was 83.8% at the cutoff value. For α-fetoprotein, the specificity was 90.8% and sensitivity was 56.8% (cutoff value 20.0 ng/ml) (20). The mRNA level of ESM-1 in tissues was correlated with the tumor-node-metastasis phase of HCC patients, tumor vascular invasion and metastasis (22).…”

“…Increased phospho-IκB and downregulated NF-κB p65 expression levels suggested that NF-κB is suppressed in ESM-1 siRNA-expressed SK-Hep1 cells, indicating that ESM-1 was able to increase the SK-Hep1 cell survival rate via the IκB-dependent NF-κB pathway. Expression of ESM-1 siRNA inhibited HCC cell migration and invasion (20). Studies have shown that endocan immune response correlates with colon tumor size, depth of invasion, lymph node metastasis, distant metastasis and Dukes' staging, and is an independent prognostic factor in disease recurrence (24).…”