Cervical Carcinoma Cells Stimulate the Angiogenesis through <scp>TSLP</scp> Promoting Growth and Activation of Vascular Endothelial Cells

Xie, Feng; Meng, Yuguang; Liu, Libing; Chang, Kai‐Kai; Li, Hui; Li, Ming‐Qing; Li, Da‐Jin

doi:10.1111/aji.12104

Cited by 46 publications

(55 citation statements)

References 41 publications

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“…A fundamental step in the transition of tumors from dormant to malignant state is followed by the potential for metastasis. Inhibiting the angiogenesis and metastasis of human cervical cancer cells could serve as an effective strategy against cervical cancer progression (Xie et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-Induced Angiogenesis in Human Cervical Cancer Cells

et al. 2014

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Metastasis is the most common cause of cancer-related death in patients, and epithelial-to-mesenchymal transition (EMT) is essential for cancer metastasis, which is a multistep complicated process that includes local invasion, intravasation, extravasation, and proliferation at distant sites. When cancer cells metastasize, angiogenesis is also required for metastatic dissemination, given that an increase in vascular density will allow easier access of tumor cells to circulation, and represents a rational target for therapeutic intervention. Berberine has several anti-inflammation and anticancer biologic effects. In this study, we provided molecular evidence that is associated with the antimetastatic effect of berberine by showing a nearly complete inhibition on invasion (P , 0.001) of highly metastatic SiHa cells via reduced transcriptional activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Berberine reversed transforming growth factor-b1-induced EMT and caused upregulation of epithelial markers such as E-cadherin and inhibited mesenchymal markers such as N-cadherin and snail-1. Selective snail-1 inhibition by snail-1-specific small interfering RNA also showed increased E-cadherin expression in SiHa cells. Berberine also reduced tumor-induced angiogenesis in vitro and in vivo. Importantly, an in vivo BALB/c nude mice xenograft model and tail vein injection model showed that berberine treatment reduced tumor growth and lung metastasis by oral gavage, respectively. Taken together, these findings suggested that berberine could reduce metastasis and angiogenesis of cervical cancer cells, thereby constituting an adjuvant treatment of metastasis control.

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Section: Introductionmentioning

confidence: 99%

Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-Induced Angiogenesis in Human Cervical Cancer Cells

et al. 2014

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“…Numerous cytokines, including VEGF, regulate the functions of vascular endothelial cells (32)(33)(34). Our previous study demonstrated that cervical cancer cells stimulate angiogenesis of vascular endothelial cells by secreting TSLP (18).…”

Section: Discussionmentioning

confidence: 99%

“…The TSLP receptor (TSLPR) is a typical heterodimeric cytokine receptor consisting of a TSLP binding subunit (TSLPRα) and the α-subunit of the IL-7 receptor (IL-7Rα) (16,17). Our previous study demonstrated that TSLP secreted by cervical cancer cells promotes angiogenesis (18). In addition, an increased level of TSLP in cancer lesions, mediated by hypoxia, was a regulator of the progression of cervical cancer, and functioned by recruiting and enabling tumor-associated eosinophils (EOS) to promote the growth of the cervical cancer cells (19).…”

Section: Introductionmentioning

confidence: 99%

TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils

et al. 2017

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Abstract. Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted by cervical cancer cells promotes angiogenesis and recruitment, and regulates the function of eosinophils (EOS). However, the function of TSLP in the crosstalk between EOS and vascular endothelial cells in cancer lesions remains unknown. The aim of the present study was to investigate the effect of EOS caused by TSLP in in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The results of the present study revealed that recombinant human TSLP protein (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF), but not fibroblast growth factors, in HL-60-eosinophils (HL-60E). Compared with cervical cancer cells (HeLa or CasKi cells) or HL-60E alone, there were increased levels of interleukin (IL)-8 and VEGF in the co-culture system between cervical cancer cells, and HL-60E cells. This effect was strengthened by rhTSLP, but inhibited by inhibiting the TSLP signal with anti-human TSLP or TSLP receptor neutralizing antibodies. The results of the tube formation assays revealed that treatment with the supernatant from cervical cancer cells and/or HL-60E resulted in an increase in angiogenesis in HUVECs, which could be decreased by TSLP or TSLPR inhibitors. The results of the present study suggested that TSLP derived of cervical cancer cells may indirectly stimulate angiogenesis of HUVECs, by upregulating IL-8 and VEGF production, in a co-culture model between cervical cancer cells and EOS, therefore promoting the development of cervical cancer.

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“…Previous studies demonstrated that H. pylori infection directly induced TSLP production from human gastric epithelial cells [12,24]. Recent research showed that TSLP could be involved in the progression of breast, lung, pancreatic, and cervical cancers; however, the regulatory mechanisms of TSLP in these cancers are not well defined [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer

et al. 2015

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Thymic stromal lymphopoietin (TSLP) is an IL-7-like type 1 inflammatory cytokine that is mainly produced by epithelial cells in the skin, lungs, thymus, and gastrointestinal tract. This cytokine is a master regulator involved in T helper 2 cell-type inflammation immune responses. Various cell types, including T, B, mast, dendritic, and cancer or cancer-associated cells, are activated via TSLP. TSLP expression is also associated with various human cancers and produced by Helicobacter pylori-infected human gastric epithelial cells. TSLP is a multi-functional protein that can act as both an oncogene and a tumor suppressor. The aim of this study was to examine the role of TSLP in the progression of gastric cancer (GC) and its correlation with clinicopathological features in GC patients. Because of the relationship between H. p ylori infection and GC, we also examined gastric tissue specimens for H. p ylori DNA. In this study, fresh tumoral tissues and distant tumor-free samples from 50 GC patients were assessed for TSLP mRNA expression by quantitative real-time PCR. The GC samples were also assessed for H. p ylori DNA using primers specific for H. p ylori 16S rRNA and the UreC genes by PCR. TSLP mRNA was overexpressed in 20 of the 50 (40%) GC samples relative to their corresponding normal tissues. TSLP overexpression was significantly correlated with tumor cell metastasis to lymph nodes. Of the 20 patients with TSLP overexpression, 17 (85.0%) had metastasis to lymph nodes (p = 0.023). In addition, the presence of H. p ylori was confirmed by PCR in 22 of the 50 (44%) cases and 10 (50%) of the 20 TSLP overexpressors. We show that human GC cells produce TSLP and a significant correlation was seen between TSLP overexpression and GC metastasis to lymph nodes. This is the first report to indicate that TSLP may play a role in lymph node involvement in GC patients.

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Cervical Carcinoma Cells Stimulate the Angiogenesis through TSLP Promoting Growth and Activation of Vascular Endothelial Cells

Abstract: This study has demonstrated that TSLP secreted by cervical carcinomas cells is involved in the angiogenesis of cervical cancer in a paracrine manner.

Cited by 46 publications

References 41 publications

Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-Induced Angiogenesis in Human Cervical Cancer Cells

Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-Induced Angiogenesis in Human Cervical Cancer Cells

TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils

Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer

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