Expression of death receptor-3 in human breast cancer and its functional effects on breast cancer cells in vitro

Abstract

Death receptor-3 (DR3) plays controversial roles in cancer. Currently, DR3 is known to be a functional receptor of vascular endothelial growth inhibitor (VEGI). The role of DR3 in breast cancer remains unclear. The present study investigated DR3 expression in a clinical cohort of breast cancer patients and its role in breast cancer cells in vitro. The expression of DR3 was examined in a breast cancer cohort using quantitative PCR (Q-PCR) and immunohistochemistry (IHC) in comparison to the patients' data. In vitro function of DR3 was examined through the targeting of this molecule in MCF7 and MDA-MB-231 breast cancer cells using ribozyme transgene technology. Decreased DR3 expression was noted in breast cancer tissues compared to normal tissues and decreased expression of DR3 was generally associated with a poorer prognosis as well as a significantly shorter long-term survival (p=0.038). Targeting of DR3 in vitro in breast cancer cell lines resulted in impaired migratory rates compared to respective control cells. Collectively, these data suggest a complex role for DR3 in breast cancer development and progression.

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease

“…Notably, a similar association with adverse outcomes appears to take place in HCC also, as it was shown that higher local or systemic DcR3 expression in this population was associated with advanced TNM stage or increased incidence of local invasion or distant metastasis [14]. A similar positive correlation of elevated DcR3 expression with unfavorable disease course was also noted not only in other neoplasms [7, 8] but also in nonneoplastic conditions [10–13]. Taken together, these results indicate that finding a highly elevated DcR3 concentration in patients with chronic inflammatory or neoplastic conditions, including chronic liver disease, may be considered a poor prognostic factor.…”

“…In addition, DcR3 has also been shown to block proinflammatory signals mediated by the aforementioned TNF/TNFRSF ligand-receptor pairs. In line with these functional data, expression studies have clearly demonstrated overexpression of DcR3 in a variety of inflammatory and neoplastic conditions [5–8]. A distinctive property of DcR3 is that it lacks a transmembrane region and exists only as soluble protein, which can be accurately determined in biological fluids [9].…”

Membrane Trafficking of Death Receptors: Implications on Signalling

“…Beside autoimmune diseases, a role for the TL1A/DR3 system in atherosclerosis [133] and tumourigenesis [145,146] has been reported. In the chemoresistant human pancreatic cancer cell line AsPC-1, DR3-induced pro-inflammatory NFκB signalling correlated with enhanced cell proliferation and invasiveness, but the underlying molecular mechanism remained unclear [145].…”

Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2

“…[7] It binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. Recent studies reported that expression of the DcR3 was minimal in normal tissues, but it was highly expressed in various types of tumors such as lung cancer,[78] esophageal cancer,[7] gastric cancer,[7] colon cancer,[7] colorectal cancer,[8] pancreatic cancer,[8] HCC,[8910] kidney cancer,[11] breast cancer,[812] ovarian cancer,[13] and skin cancer. [14] The gene was found amplified in about half of the primary lung and colon tumors studied.…”