Content area
Full Text
Introduction
Gastric cancer is a significant worldwide health issue, accounting for approximately one million new cases and more than 700,000 cancer-related deaths in 2008 (1). The majority of gastric cancer cases occurs in developing countries, and these regional variations may in part reflect differences in dietary patterns and the prevalence of Helicobacter pylori infection (2). Gastric cancer progression during the late stages significantly contributes to treatment failure, similar to most other cancers. Previous studies have shown that cancer cells obtain an interstitial cell phenotype and characteristics associated with invasive capacity via epithelial-mesenchymal transition (EMT), leading to invasion into surrounding tissues or distant organs (cancer metastasis) (3). However, to date, it remains to be defined how gastric cancer cells acquire EMT and malignant transformation. Thus, research on this topic could provide novel targets for gastric cancer treatment and prevention.
Helicobacter pylori infection plays a significant role in gastric cancer development and progression (4), while cluster of differentiation 14 (CD14) functions as a co-receptor with either Toll-like receptor TLR4 or MD-2 in the detection of bacterial lipopolysaccharide (LPS) and plays a role in the innate immune system (5,6). Another study showed that LPS, the main component of Gram-negative bacteria endotoxin, is able to induce EMT of cancer cells (7). Specifically, membrane CD14, together with TLR4, binds to LPS and transmits signals into the nucleus, activating the release of a series of cytokines (8,9), which may promote gastric carcinogenesis. For example, a previous study found that certain polymorphisms of the CD14 gene promoter region are associated with the susceptibility to gastric cancer, which could be due to alterations in CD14 expression (10).
CD14 also affects the apoptosis of cancer cells and regulates cell cycle distribution through nuclear transcription factors (11,12). These data clearly indicate that CD14 plays a role in gastric carcinogenesis; however, the underlying mechanisms remain to be determined. Thus, in the present study we aimed to ascertain whether CD14 affects gastric cancer cell EMT and invasion using shRNA technology and the underlying mechanisms responsible for CD14-mediated tumor cell EMT and invasion. These studies could provide experimental evidence for future treatment and prognosis of gastric cancer.
Materials and methods
Cell lines and culture
Gastric cancer cell lines (SGC-7901, MGC-803, BGC-823 and MKN-28) were provided by the Institute...