Endostatin expression in a pancreatic cell line is modulated by a TNFα-dependent elastase

Brammer, R D; Bramhall, Simon R.; Eggo, Margaret C.

doi:10.1038/sj.bjc.6602835

Cited by 6 publications

(4 citation statements)

References 22 publications

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“…25 The same authors have subsequently shown that collagen XVIII/endostatin mRNA is expressed in the SUIT-2 pancreatic cell line, and that endostatin is found in the cell-conditioned medium of these cells. 26 In a recent publication by Abollahi et al it has been shown that endostatin treatment of endothelial cells leads to a regulation of multiple genes in a cDNA array that potentially are involved in the angiogenic switch in vitro. Interestingly, the finding was validated in vivo in human pancreas samples including normal, inflamed and cancerous tissue.…”

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confidence: 98%

Expression pattern and circulating levels of endostatin in patients with pancreas cancer

Öhlund

Ardnor

Öman

et al. 2008

Intl Journal of Cancer

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Endostatin is a potent inhibitor of angiogenesis that is cleaved from the basement membrane protein type XVIII collagen. Expression of endostatin has recently been shown by Western blot analysis of tissue lysates in normal pancreas and pancreas cancer tissue. We show here that the expression pattern of type XVIII collagen/endostatin is shifted from a general basement membrane staining and is mainly located in the vasculature during tumor progression. This shift in type XVIII collagen/endostatin expression pattern coincides with an up-regulation of MMPs involved in endostatin processing in the tumor microenvironment, such as MMP-3, MMP-9 and MMP-13. The circulating levels of endostatin was analyzed in patients with pancreas cancer and compared to that of healthy controls, as well as after surgical treatment or in a group of nonoperable patients after intraperitoneal fluorouracil (5-FU) chemotherapy. The results show that patients with pancreas cancer have increased circulating levels of endostatin and that these levels are normalized after surgery or intraperitoneal chemotherapy. These findings indicate that endostatin could be used as a biomarker for pancreas cancer progression.

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confidence: 98%

Expression pattern and circulating levels of endostatin in patients with pancreas cancer

Öhlund

Ardnor

Öman

et al. 2008

Intl Journal of Cancer

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“…This suggested that the inhibitory effects of VEGF and bFGF siRNA on endostatin secretion may occur following its transcription and translation, and that modulating protein secretion may be its main mechanism. Brammer et al (13) confirmed that collagen XVIII is expressed in pancreatic cancer cells, and can be released into the medium. Heljasvaara et al (14) showed that particular matrix metalloproteinases (MMPs) can degrade collagen XVIII and generate biological, suggesting that endostatin is hydrolysized from collagen XVIII.…”

Section: Discussionmentioning

confidence: 98%

RNA interference-mediated silencing of VEGF and bFGF suppresses endostatin secretion in pancreatic carcinoma cells

et al. 2013

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Pro-angiogenic factors [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)] and anti-angiogenic factors (endostatin) play important roles in the progression of pancreatic cancer. The purpose of the present study was to investigate the knockdown effect by either VEGF or bFGF siRNA on the expression and secretion of endostatin in pancreatic carcinoma cells. Pancreatic carcinoma cell lines (sw1990, Panc-1 and PCT-3) were treated with VEGF and bFGF siRNA. The expression of VEGF, bFGF and endostatin in pancreatic carcinoma cell lines was determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Secretion of endostatin was measured by enzyme-linked immunosorbent assay (ELISA). bFGF and VEGF siRNA significantly reduced the expression of bFGF and VEGF mRNA, respectively, but did not affect mRNA and protein expression of endostatin in pancreatic carcinoma cell lines. However, secretion of endostatin in PCT-3, Panc-1 and sw1990 cells was significantly inhibited by bFGF and VEGF siRNA. This study demonstrated that pro-angiogenic factors (VEGF and bFGF) differentially modulate expression and secretion of anti-angiogenic factors (endostatin). This result may have important implications in the anti-angiogenesis therapy in pancreatic cancer.

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“…Production of endostatin is dependent on the action of tumor infiltrating macrophages that secrete elastases, which in turn act on collagen XVIII, leading to the release of a bioactive protein fragment (40). Cytokines, such as the proinflammatory TNF-␣, interfere with the yield of endostatin production (41). It is still not clear whether all circulating endogenous endostatin is functional.…”

Section: Discussionmentioning

confidence: 99%

Anti‐tumor effect of endostatin mediated by retroviral gene transfer in mice bearing renal cell carcinoma

et al. 2007

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We investigated whether transfer of the gene encoding the angiogenesis inhibitor endostatin into the NIH/3T3 fibroblast cell line could inhibit renal tumor growth in vivo. NIH/3T3 cells were transduced with retroviral vectors containing the murine endostatin (ES) gene. SCID mice bearing CaKi-1 derived tumors were given a subcutaneous injection of either ES-transduced cells or control cells and were monitored for tumor growth. At the end of the in vivo experiment, the mean tumor volume of treated mice was 51.6 +/- 2.4 mm3, while the tumor volume of control was 234.5 +/- 14.8 mm3. Microvascular density was significantly decreased on treatment (control 9.79 vs. ES 2.53%, <0.001) accompanied by a 23-fold increase in intratumoral necrotic area and a 2.94-fold increase in the apoptotic index, determined by immunohistochemistry with anti-activated caspase-3. Apoptotic cells were found in foci enriched in infiltrating leukocytes. In conclusion, retroviral endostatin gene transfer led to secretion of functional endostatin that was sufficiently active to inhibit tumor angiogenesis and tumor growth. A second mechanism may also be implied in endostatin-dependent tumor regression, associated with tumor infiltration of leukocytes. Besides its antiangiogenic properties, endostatin may be a promising adjuvant to immunotherapy.

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Endostatin expression in a pancreatic cell line is modulated by a TNFα-dependent elastase

Cited by 6 publications

References 22 publications

Expression pattern and circulating levels of endostatin in patients with pancreas cancer

Expression pattern and circulating levels of endostatin in patients with pancreas cancer

RNA interference-mediated silencing of VEGF and bFGF suppresses endostatin secretion in pancreatic carcinoma cells

Anti‐tumor effect of endostatin mediated by retroviral gene transfer in mice bearing renal cell carcinoma

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