Characterization of recombinant soluble human transforming growth factor-β receptor Type II (rhTGF-βsRII)

Tsang, Monica; Zhou, Li; Zheng, Bo-Ling; Wenker, Jeff; Fransen, Greg; Humphrey, J. A. C.; Smith, John L.; O’Connor-McCourt, Maureen D.; Lucas, Robert A.; Weatherbee, James A.

doi:10.1006/cyto.1995.0054

Cited by 70 publications

(60 citation statements)

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“…A 4000-fold excess of recombinant solRII to TGF-␤ was able to completely neutralize TGF-␤ activity. This is well in range with other studies in which a 1,600-to 20,000-fold excess of solRII was needed to fully inhibit TGF-␤ activity (25,29). The solRII obtained from the osmotic pumps retrieved from the mice after implantation showed no loss of blocking activity compared with freshly produced solRII.…”

Section: Discussionsupporting

confidence: 88%

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Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Scharstuhl

Glansbeek

Beuningen

et al. 2002

The Journal of Immunology

218

157

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Osteoarthritis has as main characteristics the degradation of articular cartilage and the formation of new bone at the joint edges, so-called osteophytes. In this study enhanced expression of TGF-β1 and -β3 was detected in developing osteophytes and articular cartilage during murine experimental osteoarthritis. To determine the role of endogenous TGF-β on osteophyte formation and articular cartilage, TGF-β activity was blocked via a scavenging soluble TGF-β-RII. Our results clearly show that inhibition of endogenous TGF-β nearly completely prevented osteophyte formation. In contrast, treatment with recombinant soluble TGF-β-RII markedly enhanced articular cartilage proteoglycan loss and reduced the thickness of articular cartilage. In conclusion, we show for the first time that endogenous TGF-β is a crucial factor in the process of osteophyte formation and has an important function in protection against cartilage loss.

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Section: Discussionsupporting

confidence: 88%

“…We chose the extracellular part of TGF-␤-RII as a TGF-␤ antagonist because it has a very high affinity for TGF-␤1 and -␤3 (24,25), which are both abundantly present in the joint (12,26,27). Moreover, because of its small size of 25 kDa, solRII can penetrate cartilage and directly affect chondrocytes (28).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Scharstuhl

Glansbeek

Beuningen

et al. 2002

The Journal of Immunology

218

157

View full text Add to dashboard Cite

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“…For inhibition of TGF-b signaling, PDAC cells were co-cultured with PSCs as described above, and treated with recombinant human TGF-b sRII/Fc (rhTbsR-II) (100 ng/ml, 341-BR, R&D Systems), 32 TGF-b neutralizing antibody (10 mg/ml, MAB1835, R&D Systems) or mouse control IgG1 (10 mg/ml, MAB002, …”

Section: Inhibition Of Tgf-b Signaling Using Neutralizing Antibodymentioning

confidence: 99%

Anterior gradient 2 downregulation in a subset of pancreatic ductal adenocarcinoma is a prognostic factor indicative of epithelial–mesenchymal transition

Mizuuchi

Aishima

Ohuchida

et al. 2015

Laboratory Investigation

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Anterior gradient 2 (AGR2), a member of the protein disulfide isomerase family, has been implicated in various cancers including pancreatic ductal adenocarcinoma (PDAC) and is known to promote cancer progression. However, the prognostic value of AGR2 expression and the interaction with epithelial-mesenchymal transition (EMT) remain unclear. We investigated the clinical significance of AGR2 and EMT markers in PDAC patients by immunohistochemical analyses. Although AGR2 expression was not observed in normal pancreas, all pancreatic precursor neoplastic lesions were positive for AGR2, even at the earliest stages, including pancreatic intraepithelial neoplasia-1A, AGR2 expression was reduced in 27.7% (54/195 cases) of PDAC patients. AGR2 downregulation correlated with EMT markers (vimentin overexpression and reduced membranous E-cadherin expression), high Union for International Cancer Control stage (Po0.0001), high histological cellular grade (Po0.0001), and adverse outcome (Po0.0001). In vitro, targeted silencing of AGR2 in cancer cells using siRNA reduced cell proliferation, colony formation, cell invasiveness, and migration, but did not alter EMT markers. To confer a more aggressive phenotype and induce EMT in PDAC cells, we co-cultured PDAC cell lines with primary-cultured pancreatic stellate cells (PSCs) and found that AGR2 was downregulated in co-cultured PDAC cells compared with PDAC monocultures. Treatment with transforming growth factor beta-1 (TGF-b), secreted from PSCs, decreased AGR2 expression, whereas inhibition of TGF-b signaling using recombinant soluble human TGF-b receptor type II and TGF-b-neutralizing antibodies restored AGR2 expression. We conclude that AGR2 downregulation is a useful prognostic marker, induced by EMT, and that secreted TGF-b from PSCs may partially contribute to AGR2 downregulation in PDAC patients. AGR2 downregulation does not induce EMT or a more aggressive phenotype, but is a secondary effect of these processes in advanced PDAC.

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“…Recombinant TGF-b1 used in this study was reported to function on murine-derived cell lines. 35 TGF-b1 treatment on cell proliferation study of HuH28 was started at about 50% celldensity, because HuH28 had low-proliferative activity (doubling time: 7 days).…”

Section: Cell Culture Studiesmentioning

confidence: 99%

Intrahepatic cholangiocarcinoma escapes from growth inhibitory effect of transforming growth factor-β1 by overexpression of cyclin D1

Zen

Harada

Sasaki

et al. 2005

Laboratory Investigation

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Transforming growth factor-b1 (TGF-b1) is involved in tumor progression by promoting angiogenesis or suppressing the immune system; yet TGF-b1 also has a growth-inhibitory effect on epithelial cells including carcinoma cells. Several mechanisms of impaired TGF-b1 responsiveness of carcinoma cells have been reported. In this study, we examined how TGF-b1 participates in the development and progression of intrahepatic cholangiocarcinoma (ICC) associated with hepatolithiasis, and how ICC cells escape from growth inhibitory effect of TGF-b1. A total of 40 cases of hepatolithiasis were studied, including 16 cases of ICC, and in vitro studies were conducted with cultured murine non-neoplastic biliary epithelial cells (MBEC) and three ICC cell lines. Immunohistochemically, TGF-b1 was expressed in mononuclear cells and mesenchymal cells around the stone-containing bile ducts and invasive ICC, and also in biliary epithelial cells (hyperplastic and precursor lesions, and ICC). TGF-b type II receptor (TbR-II) was constantly expressed on biliary epithelial cells irrespective of biliary lesions. In cell culture studies, TGF-b1 significantly inhibited proliferation of MBEC via downregulation of cyclin D1, cdk4, and cdk6, while TGF-b1 did not influence the proliferation of ICC cells. After suppression of cyclin D1 expression in one ICC cell line using cyclin D1 small interfering RNA, TGF-b1 significantly inhibited the proliferation of ICC cells. In conclusion, high levels of TGF-b1 around ICC or its precursors may be involved in development and progression of ICC in hepatolithiasis. ICC cells could escape the growth inhibitory effect of TGF-b1 by overexpression of cyclin D1.

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Characterization of recombinant soluble human transforming growth factor-β receptor Type II (rhTGF-βsRII)

Cited by 70 publications

References 0 publications

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Anterior gradient 2 downregulation in a subset of pancreatic ductal adenocarcinoma is a prognostic factor indicative of epithelial–mesenchymal transition

Intrahepatic cholangiocarcinoma escapes from growth inhibitory effect of transforming growth factor-β1 by overexpression of cyclin D1

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