Biglycan up-regulated vascular endothelial growth factor (VEGF) expression and promoted angiogenesis in colon cancer

Xing, Xiaojing; Gu, Xiaohu; Ma, Tianfei; Ye, Hui-Nan

doi:10.1007/s13277-014-2779-y

Cited by 58 publications

(54 citation statements)

References 27 publications

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“…Interestingly, NF‐kB is an essential component in the TLR signaling pathway (Xiao and Ghosh, 2005). Studies have shown that BGN can upregulate VEGF expression and promote angiogenesis in colon cancer (Xing et al., 2015), which is consistent with our previous findings that BGN could stimulate tubular formation activity in HUVECs. Nevertheless, the exact mechanism through which BGN regulates VEGF expression remains unclear.…”

Section: Introductionsupporting

confidence: 93%

Biglycan stimulates VEGF expression in endothelial cells by activating the TLR signaling pathway

Zang

Wang

et al. 2016

Molecular Oncology

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Biglycan (BGN) is an important component of the extracellular matrix (ECM) that is impli-cated in a variety of human cancers. In our previous study, we reported that BGN was overexpressed in gastric cancer (GC) tissues and promoted cancer metastasis. Moreover, the tubular formation capacity in HUVECs was promoted by stimulation with culture media from BGN-overexpressing GC cells, but the exact underlying mechanism is still unknown.The purpose of this study was to determine the role and molecular mechanism of BGN in VEGF expression in endothelial cells. We found that BGN stimulation of endothelial cells increased the interaction between NF-kB and the HIF-1a promoter, leading to enhanced promoter activity and increased HIF-1a mRNA levels, as well as augmented HIF-1 activity that resulted in VEGF expression. All of this was dependent on the interaction of BGN with its receptors, TLR2 and TLR4. Moreover, we found that BGN enhanced endothelial cell migration and proliferation, as well as tube formation, in a TLR signaling pathwaydependent manner. In addition, endothelial cell-derived VEGF in turn was found to act on GC cells and promotes their migration. The combined findings of our current and previous studies suggest that BGN secreted from GC cells into the tumor stroma promotes GC development, as well as its progression, potentially through the chronic activation of tumor angiogenesis. ª 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. IntroductionGastric cancer (GC) poses a great threat to the health of people worldwide and ranks third among all types of tumors in China (Piazuelo and Correa, 2013). Therefore, it is of great importance to explore the mechanisms of the occurrence and development of GC. Studies have proven that tumor inflammation is a key component of the tumor microenvironment, which contributes to tumor proliferation, survival and invasion (Mantovani et al., 2008). The most important factor causing inflammation in GC may be Helicobacter pylori (HP) infections (Horemans et al., 2016;Kazemi et al., 2016;Liang et al., 2014), especially with HP containing a contiguous cag pathogenicity island (cag-PAI), which encodes a known virulence factor,

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Section: Introductionsupporting

confidence: 93%

Biglycan stimulates VEGF expression in endothelial cells by activating the TLR signaling pathway

Zang

Wang

et al. 2016

Molecular Oncology

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“…These results were consistent with previously published results, which demonstrated that biglycan may promote cell proliferation and the migratory abilities of cells (25,26). Furthermore, these results indirectly support our previous findings that biglycan overexpression promoted xenograft colon tumor growth, and that the upregulation of biglycan was associated with the malignancy in human colorectal cancer (13,27). The results of the present study indicated that biglycan has an oncogenic role in the colon cancer process, which is associated with regulating the proliferation, migration and invasion of colon cancer cells.…”

Section: Discussionsupporting

confidence: 93%

Knockdown of biglycan expression by RNA interference inhibits the proliferation and invasion of, and induces apoptosis in, the HCT116 colon cancer cell line

Xing

2015

Molecular Medicine Reports

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Abstract.Biglycan is an important component of the extracellular matrix, and it is also a member of small leucine-rich proteoglycan family. Previous studies indicated that the expression of biglycan was increased in a variety of tumor tissues, including colon cancer. However, the mechanisms underlying its effects in colon cancer remain to be fully elucidated. In the present study, the effects of biglycan knockdown on colon cancer cell proliferation, migration, invasion and apoptosis were investigated. The mRNA expression levels of biglycan in the HCT116 colon cancer cell line were downregulated using RNA interference, and the stably transfected cell line was obtained through G418 screening for subsequent experiments. The results revealed that downregulation of the expression of biglycan suppressed cell proliferation and caused a cell cycle arrest at the G0/G1 phase. The results of the western blot analysis also revealed that the expression levels of cell cycle-associated proteins, including cyclin A and cyclin D1, were markedly decreased following silencing of biglycan, whereas the expression levels of p21 and p27 were markedly increased compared with that of the short hairpin RNA control group. Furthermore, the decreased expression of biglycan inhibited colon cancer cell migration and invasion, and induced apoptosis. A complete inhibition of the p38 signaling pathway with SB203580 effectively reversed the increase in apoptotic cell numbers induced by biglycan downregulation. Taken together, the results of the present study indicated that biglycan exerts an important role in cell proliferation, migration, invasion and apoptosis in colon cancer, and that biglycan regulates the p38 MAPK signaling pathway by exerting an antiapoptotic effect. Therefore, biglycan may represent a putative target for colon cancer gene therapy.

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“…ECM reorganization is strongly interlinked with angiogenesis and related proteins were found regulated in both cell types as well. Biglycan is a structural component of the ECM but also contributes to blood vessel remodeling, apparently being able to upregulate the expression of VEGF and thus promoting angiogenesis (55). Indeed, this protein, when proteolytically released from the ECM, acts as a danger signal stimulating pro-inflammatory signaling and activating the inflammasome (56).…”

Section: Discussionmentioning

confidence: 99%

Contribution of Human Fibroblasts and Endothelial Cells to the Hallmarks of Inflammation as Determined by Proteome Profiling

Slany

Bileck

Kreutz

et al. 2016

Molecular & Cellular Proteomics

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In order to systematically analyze proteins fulfilling effector functionalities during inflammation, here we present a comprehensive proteome study of inflammatory activated primary human endothelial cells and fibroblasts. Cells were stimulated with interleukin 1-␤ and fractionated in order to obtain secreted, cytoplasmic and nuclear protein fractions. Proteins were submitted to a data-dependent bottom up analytical platform using a QExactive orbitrap and the MaxQuant software for protein identification and label-free quantification. Results were further combined with similarly generated data previously obtained from the analysis of inflammatory activated peripheral blood mononuclear cells. Applying a false discovery rate of less than 0.01 at both, peptide and protein level, a total of 8370 protein groups assembled from 117,599 peptides was identified; mass spectrometry data have been made fully accessible via ProteomeXchange with identifier PXD003406 to PXD003417. Comparative proteome analysis allowed us to determine common and cell type-specific inflammation signatures comprising novel candidate marker molecules and related expression patterns of transcription factors. Cardinal features of inflammation such as interleukin 1-␤ processing and the interferon response differed substantially between the investigated cells. Furthermore, cells also exerted similar inflammation-related tasks; however, by making use of different sets of proteins. Hallmarks of inflammation thus emerged, including angiogenesis, extracellular matrix reorganization, adaptive and innate immune responses, oxidative stress response, cell proliferation and differentiation, cell adhesion and migration in addition to monosaccharide metabolic processes, representing both, common and cell type-specific responsibilities of cells during inflammation. Molecular & Cellular

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Biglycan up-regulated vascular endothelial growth factor (VEGF) expression and promoted angiogenesis in colon cancer

Cited by 58 publications

References 27 publications

Biglycan stimulates VEGF expression in endothelial cells by activating the TLR signaling pathway

Biglycan stimulates VEGF expression in endothelial cells by activating the TLR signaling pathway

Knockdown of biglycan expression by RNA interference inhibits the proliferation and invasion of, and induces apoptosis in, the HCT116 colon cancer cell line

Contribution of Human Fibroblasts and Endothelial Cells to the Hallmarks of Inflammation as Determined by Proteome Profiling

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