Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells

Yamamoto, Kazuhiro; Ohga, Noritaka; Hida, Kyoko; Maishi, Nako; Kawamoto, Taisuke; Kitayama, Kenji; Akiyama, Kosuke; Osawa, Takahiro; Kondoh, Miyako; Matsuda, Kohei; Onodera, Yasuhito; Fujie, Manabu; Kaga, Kichizo; Hirano, Satoshi; Shinohara, Nobuo; Shindoh, Masanobu

doi:10.1038/bjc.2012.59

Cited by 90 publications

(135 citation statements)

References 37 publications

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“…The proportion of cells in the G0/G1 phase was significantly increased, and the expression levels of the cell cycle-associated proteins, cyclins A and D1, were downregulated, whereas the levels of their inhibitory proteins, p21 and p27, were upregulated. 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).…”

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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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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“…Furthermore, in both mouse and human TECs(tumor endothelial cells), BGN was highly expressed, and TEC migration was inhibited after knocking down the BGN. During tumor angiogenesis, the BGN is activated, so it might be a new marker of TECs and may contribute to the anti-angiogenic therapy [27].…”

Section: Discussionmentioning

confidence: 99%

“…BGN, constitutively expressed in normal endothelial cells, becomes significantly overexpressed in tumor tissues and promotes the migration of endothelial cell and neovascularization of cancer [28]. With similar mechanisms, BGN is able to triggering VEGF synthesis in tumor cells, and it has been shown to bind and sequester (VEGFA) in the ECM, thus generating a reservoir of VEGF that can be released during ECM degradation that associated with tumor, capacitating angiogenesis [29].…”

Section: Discussionmentioning

confidence: 99%

Biglycan enhances the ability of migration and invasion in endometrial cancer

Sun

Wang

Han

et al. 2015

Arch Gynecol Obstet

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“…Clinical studies have shown that biglycan expression is elevated in hepatocellular carcinoma [7], ovarian carcinoma [8], endometrial cancer [9], pancreatic cancer [10], gastric cancer [11], and colon cancer [12] and that biglycan up-regulation is associated with poor prognosis [13,14]. Recent studies have demonstrated that biglycan expression is significantly higher in tumor vascular tissue than in normal vascular tissue; therefore, biglycan can be used as a marker of tumor endothelial cells involved in neovascularization [15]. However, whether it involves in and the underlying mechanism of tumor angiogenesis requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

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

Xing

et al. 2014

Tumor Biol.

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Biglycan is an important component of the extracellular matrix, which belongs to the small leucine-rich proteoglycan family. Recent studies have shown that biglycan expression is elevated in many tumor tissues and implies poor prognosis, such as colon cancer. However, the molecular mechanism of biglycan in colon cancer has not been investigated. The present study aimed to investigate the effects of biglycan on vascular endothelial growth factor (VEGF) expression in colon cancer cells and on tumor angiogenesis in vivo. Biglycan overexpression vectors were constructed, and the stable biglycan overexpression in human colon cancer cell lines (HCT116 cells) was established by G418 screening. The stable cell clones were subsequently used to initiate tumor xenografts in nude mice. Our results showed that biglycan overexpression notably up-regulated the levels of VEGF in colon cancer cells, which was further confirmed by immunohistochemistry analysis in the xenograft colon tumors. Moreover, high levels of biglycan promoted angiogenesis and colon tumor growth, as evidenced by the increased cell viability, colon tumor size, and weight, as well as the CD34 expression. Additionally, we found that the extracellular signal-regulated kinase (ERK) signaling pathway was activated by biglycan in colon cancer cells. The ERK inhibitor PD98059 dramatically reversed the increased expression of VEGF induced by biglycan. Taken together, our results indicated that biglycan up-regulated VEGF expression in colon cancer cells and promoted tumor angiogenesis. Biglycan-mediated VEGF regulation may correlate with the activation of the ERK signaling pathway. Therefore, biglycan may be a promising target for anti-angiogenic therapy for cancer.

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Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells

Cited by 90 publications

References 37 publications

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

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

Biglycan enhances the ability of migration and invasion in endometrial cancer

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

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