Effects of receptor for advanced glycation endproducts on microvessel formation in endometrial cancer

Abstract

BackgroundThe receptor for advanced glycation endproducts (RAGE) and microvascular status both play a critical role in cancer progression. However, the crosstalk between RAGE and microvascular formation in endometrial cancer remains largely unknown.MethodsRAGE expression and microvessel density were examined in 20 cases of normal endometrial tissue, 37 cases of well-differentiated endometrial cancer tissue, and 35 cases of poorly-differentiated endometrial cancer tissue. Regression analysis was used to examine the relationship between RAGE and microvessel density. The knockdown of RAGE was achieved using a small interfering RNA in HEC-1A endometrial cancer cells. A xenografted tumour model was used to evaluate RAGE-mediated microvascular formation and proliferation of endometrial cancer cells.ResultsIt was shown that (i) RAGE expression gradually increased in normal endometrium, well-differentiated endometrial cancer, and poorly-differentiated endometrial cancer, respectively; (ii) a positive correlation existed between RAGE and microvessel density in human endometrial cancer samples; (iii) RAGE knockdown was effective in decreasing microvessel formation in xenografted tumour models; and (iv) RAGE knockdown can significantly inhibit the proliferation of endometrial cancer cells in vivo.ConclusionsThese results indicate that RAGE may be a potential trigger in microvascular formation and proliferation in the development of endometrial cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2126-3) contains supplementary material, which is available to authorized users.

AGER promotes proliferation and migration in cervical cancer

“…AGER-deficient mice presented a decreased tendency for breast tumor growth [ 8 ] and AGER gene deletion inhibited the development of pancreatic intraepithelial neoplasia and progression to pancreatic ductal adenocarcinoma in a murine model [ 23 ]. Similar results were reported in endometrial cancer [ 15 ], colorectal cancer [ 18 ], and prostate cancer [ 24 ].…”

“…It plays decisive roles in diverse processes including inflammation and cancer [ 9 , 10 ]. AGER has been widely reported to be overexpressed in ovarian cancer [ 12 ], breast cancer [ 13 ], gastric cancer [ 14 ], colorectal cancer [ 21 ], and endometrial cancer [ 15 ]. With regard to cervical cancer, Xu et al [ 22 ] reported that AGER 82G>S polymorphisms were associated with significantly elevated risk of cervical cancer.…”

“…AGER engagement activates multiple intracellular signaling mechanisms that fuel chronic inflammatory conditions leading to malignant transformation [ 9 , 10 ]. Indeed, AGER has been widely reported being highly expressed in various types of cancer, including ovarian cancer [ 12 ], breast cancer [ 13 ], gastric cancer [ 14 ], and endometrial cancer [ 15 ]. It is well documented that AGER plays specific roles in the modulation of several cellular events, including proliferation [ 16 ], cell motility [ 17 ], and angiogenesis [ 18 , 19 ].…”

Identification of genes associated with cancer progression and prognosis in lung adenocarcinoma: Analyses based on microarray from Oncomine and The Cancer Genome Atlas databases

“…AGER is one of a limited number of pathogen recognition receptors whose expression is downregulated in lung cancer (Rho, Roehrl, & Wang, 2009;Wang, Li, Yu, et al, 2015). However, AGER has been widely reported being highly expressed in various types of cancer, including ovarian cancer (Rahimi et al, 2017), breast cancer (Nankali et al, 2016), gastric cancer (Wang, Li, Ye, et al, 2015), and endometrial cancer (Zheng et al, 2016). In the current study, we found AGER was significantly and consistently downregulated at least 8.266-fold in LUAD according to four independent microarrays databases.…”

Immunomodulatory Factors in Primary Endometrial Cell Cultures Isolated from Cancer and Noncancerous Human Tissue–Focus on RAGE and IDO1

“…Contribution of surface receptor RAGE signaling is an additional component contributing to endometrial microenvironment [ 25 , 26 , 27 ]. This is a transmembrane receptor expressed on several cell types, including epithelial, endothelial, and immune cells activating migration, proliferation, and inflammatory response [ 26 , 28 , 29 , 30 , 31 ].…”