The Role Of Biglycan In The Progression Of Endometrial Cancer

Objective:Endometrial cancer is one of the three malignant tumors of femalegenital tract, and its incidence shows a rising trend in recent years. Like other malignant tumors, endometrial cancer is caused by the regulation dysfunction of variety of factors, leading to the imbalance between cell proliferation and death, which causes cell abnormal proliferation and continued division, and ultimately resulting in carcinogenesis. Biglycan (BGN) belongs to a member of the small leucine-rich proteoglycans (SLRPs) that is a component of the extracellular matrix. Biglycan has been found in almost every organ within our body, but it is not uniformly distributed within an organ. Biglycan has been shown to be expressed on the cell surface, and sometimes within the extracellular matrices of a range of specialized cell types within the organ. Its expression pattern has been shown to be altered by growth factors and certain pathologic conditions. Recently higher expression of BGN has been detected in several tumor tissue compared with the normal tissue such as pancreatic adenocarcinoma, colon tumor, ovary cancer, intrahepatic cholangiocarcinoma and gastric cancer. The over-expression of BGN in tumor tissues suggesting an significant role of BGN in cancer metastasis and progression. Our studies have confirmed the elevated expression of BGN in endometrial cancer, revealing its significance in the progression of endometrial cancer, but the concrete role of BGN remains unknown. Therefore, the objective of the study is to investigate the effect of BGN on endometrial cancer in vivo and in vitro,.Methods:Western blotting and polymerase chain reaction (PCR) were used toscreen out the BGN overexpressed endometrial cancer cell line, and stable BGN knock-out cell line was constructed by lentivirus transfection. Wound healing was used to test the ability of BGN to recover the endometrial cancer cells. Transwell chamber was used to test the change of migration and invasion of endometrial cancer cells. Tube formation was used to test the effect of BGN on endometrial cancer cells angiogenesis in vitro. In animal experiment, intraperitoneal endometrial cancer Xenograft model was established, and injected the single cell suspension of logarithmic growth control group Ishikawa/vector and experimental group Ishikawa/shBGN in the abdominal cavity of 4-week old female BALB/C-nu/nu nude mice,10 nude mice in each group. Nude mice were suffocated with CO2 after 40 days. Tumor was separated, weighted and formalin-fixed preserved. Immunohistochemistry(IHC) and HE staining detected tumors to test the effect of BGN on migration and invasion of endometrial cancer in vivo. SPSS 13.0 statistical software was used to statistically evaluate all data, two-tailed test, a difference of P<0.05 was considered significant. All quantitative data were expressed as mean value±standard deviation.Results:(1) BGN expression level is significantly higher in the Ishikawa and AN3CA cells than in other endometrial cancer cells.(2) We have established stable BGN knock-out endometrial cancer cell line, and the expression of BGN in Ishikawa/shBGN is evidently lower than in Ishikawa/vector.(3) Using wound healing, transwell chamber and tube formation assay, we confirm that BGN enhances the metastasis, migration and angiogenesis abilities of endometrial cancer cells. In animal experiment, more intraperitoneal tumors are generated in experimental group Xenograft model (P<0.05), which has confirmed the outcome in vivo.Conclusions:(1) BGN might act as an oncogene in endometrial cancer, and it plays an important role in the progression of endometrial cancer.(2) BGN might be an important target for the molecular therapy of advanced and recurrence endometrial cancer, which has significance in the treatment of endometrial cancer.