Down-Regulated Proteins of Mesenchymal Tumor Cells

Schenker, Thomas; Trüeb, Beat

doi:10.1006/excr.1997.3896

Cited by 48 publications

(40 citation statements)

References 36 publications

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“…TGF-b acts as a tumor suppressor by inhibiting cellular proliferation or by promoting cellular differentiation or apoptosis (Epstein, 2000). Although the role of big-h3 in tumors has not been extensively studied, it has been reported to be downregulated in mesenchymal tumor cells (Schenker and Trueb, 1998) and rhabdomyosarcoma (Genini et al, 1996). Our observations suggest that the TGFb-induced-big-h3 could be a mechanism mediating TGF-b-mediated tumor suppression and that it may act as a tumor suppressor.…”

Section: Discussionmentioning

confidence: 63%

RGD peptides released from βig-h3, a TGF-β-induced cell-adhesive molecule, mediate apoptosis

Kim

Jeong

et al. 2003

Oncogene

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big-h3 is a transforming growth factor-b (TGF-b)-induced cell-adhesive molecule and has an RGD sequence at its Cterminus. A previous report suggested that big-h3 normally undergoes carboxy-terminal processing that results in the loss of the RGD sequence. RGD peptides appear to play various roles in cell function. Here we show that the RGD peptides released from big-h3 may facilitate TGF-b-induced apoptosis. We found that carboxy-terminal cleavage of big-h3 occurred after its secretion, and that overexpression of the wild-type big-h3 induced apoptosis, unlike the C-terminal deleted but RGDcontaining mutant big-h3, which is resistant to C-terminal processing. The big-h3-induced apoptosis was abolished by either deletion of the RGD sequence or mutation of RGD to RAE. Synthetic peptides of ERGDEL and GRGDSP derived from big-h3 and fibronectin, respectively, also induced apoptosis, unlike ERGEEL and GRGESP. Culture supernatants of cells overexpressing big-h3 filtered to isolate molecules smaller than 3 kDa also induced apoptosis. A fusion protein composed of the N-terminal 100 amino acids of fibronectin and the RGDcontaining C-terminal part of big-h3 was also subjected to C-terminal cleavage and overexpression resulted in apoptosis. The anti-big-h3 antibody blocks TGF-binduced apoptosis. Thus, big-h3 may be important in regulating cell apoptosis by providing soluble RGD peptides.

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Section: Discussionmentioning

confidence: 63%

RGD peptides released from βig-h3, a TGF-β-induced cell-adhesive molecule, mediate apoptosis

Kim

Jeong

et al. 2003

Oncogene

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“…Altered expression of a series of genes that controlled cellular growth and differentiation between these two cell models was found (Zhao et al, 2001), with Betaig-h3 gene notably downregulated in tumour cells, a finding that was further confirmed in five tumour cell lines by Northern blot. Previous studies have shown that Betaig-h3 gene is significantly reduced in embryonal rhabdomyosarcoma cell lines and mesenchymal tumours (Genini et al, 1996;Schenker and Trueb, 1998), suggesting that Betaig-h3 may have an important role in human cancer. Although overexpression of this gene in CHO fibroblast cells leads to a marked decrease in their ability to form tumour in nude mice (Skonier et al, 1994), little is known about its regulation in tumour progression of human tissues.…”

Section: Discussionmentioning

confidence: 96%

Overexpression of Betaig-h3 gene downregulates integrin α5β1 and suppresses tumorigenicity in radiation-induced tumorigenic human bronchial epithelial cells

2002

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{Interaction between cell and extracellular matrix plays a crucial role in tumour invasion and metastasis. Using an immortalised human bronchial epithelial (BEP2D) cell model, the study here shows that expression of Betaig-h3 gene, which encodes a secreted adhesion molecule induced by transforming growth factor-b, is markedly decreased in several independently generated, radiation-induced tumour cell lines (TL1 -TL5) relative to parental BEP2D cells. Transfection of Betaig-h3 gene into tumour cells resulted in a significant reduction in tumour growth. While integrin receptor a5b1 was overexpressed in tumour cells, its expression was corrected to the level found in control BEP2D cells after Betaig-h3 transfection. These data suggest that Betaig-h3 gene is involved in tumour progression by regulating integrin receptor a5b1. The findings provide strong evidence that the Betaig-h3 gene has tumour suppressor function in human BEP2D cell model and suggest a potential target for interventional therapy.

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“…Following isolation on RNeasy columns, the purified RNA was resolved on 1% agarose gels in the presence of 1% formaldehyde and transferred to nylon membranes by vacuum blotting. Radioactively labeled cDNA probes were hybridized at 42°C to the membranes in a buffer containing 50% formamide as described (9,10). Following stringent washing, the membranes were exposed to x-ray film.…”

Section: Methodsmentioning

confidence: 99%

“…Two subtracted cDNA libraries were constructed by the biotin/streptavidin/phenol method (10,11). In brief, the poly(A) RNA isolated from embryonic chicken sterna and from embryonic chicken control tissues (skin and skeletal muscle) was transcribed separately into double stranded cDNA and provided with specific adapters.…”

Section: Methodsmentioning

confidence: 99%

Characterization of FGFRL1, a Novel Fibroblast Growth Factor (FGF) Receptor Preferentially Expressed in Skeletal Tissues

Trüeb

Zhuang

Taeschler

et al. 2003

Journal of Biological Chemistry

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Clones for a novel transmembrane receptor termed FGFRL1 were isolated from a subtracted, cartilage-specific cDNA library prepared from chicken sterna. Homologous sequences were identified in other vertebrates, including man, mouse, rat and fish, but not in invertebrates such as Caenorhabditis elegans and Drosophila. FGFRL1 was expressed preferentially in skeletal tissues as demonstrated by Northern blotting and in situ hybridization. Small amounts of the FGFRL1 mRNA were also detected in other tissues such as skeletal muscle and heart. The novel protein contained three extracellular Ig-like domains that were related to the members of the fibroblast growth factor (FGF) receptor family. However, it lacked the intracellular protein tyrosine kinase domain required for signal transduction by transphosphorylation. When expressed in cultured cells as a fusion protein with green fluorescent protein, FGFRL1 was specifically localized to the plasma membrane where it might interact with FGF ligands. Recombinant FGFRL1 protein was produced in a baculovirus system with intact disulfide bonds. Similar to FGF receptors, the expressed protein interacted specifically with heparin and with FGF2. When overexpressed in MG-63 osteosarcoma cells, the novel receptor had a negative effect on cell proliferation. Taken together our data are consistent with the view that FGFRL1 acts as a decoy receptor for FGF ligands.Most bones of the vertebrate skeleton are formed by a complex process termed endochondral ossification which involves a cartilage intermediate (1). This intermediate represents a highly specialized connective tissue. It consists of a single cell type, the chondrocytes, which are embedded in a rich extracellular matrix (2). Typically, this matrix makes up more than 90% of the cartilage volume and consists of collagens (types II, IX, X, and XI), proteoglycans (aggrecan, small leucine-rich proteins), and glycoproteins (matrilins, COMP).During the first step of endochondral ossification, mesenchymal cells condense and differentiate into chondrocytes (3). These chondrocytes proliferate rapidly and lay down the cartilaginous model of the future bones. The chondrocytes undergo a complex series of distinct developmental stages, including proliferation, maturation, and hypertrophy. The hypertrophic cartilage is calcified and becomes vascularized. Finally, the calcified cartilage is invaded by osteoclasts and osteoblasts, which replace the cartilaginous tissue by bone.Cartilage has become a popular tissue to study cell proliferation and differentiation in vitro (3). When cultivated on plastic dishes, chondrocytes rapidly dedifferentiate into fibroblast-like cells. In three-dimensional lattices, however, the chondrocytes undergo the ordered sequence of events observed during differentiation and maturation of cartilage in vivo. Three stages of chondrocyte differentiation have been defined in vitro: proliferative chondrocytes producing mainly collagen II, hypertrophic chondrocytes producing collagen X, and osteoblast-like cells producing...

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Down-Regulated Proteins of Mesenchymal Tumor Cells

Cited by 48 publications

References 36 publications

RGD peptides released from βig-h3, a TGF-β-induced cell-adhesive molecule, mediate apoptosis

RGD peptides released from βig-h3, a TGF-β-induced cell-adhesive molecule, mediate apoptosis

Overexpression of Betaig-h3 gene downregulates integrin α5β1 and suppresses tumorigenicity in radiation-induced tumorigenic human bronchial epithelial cells

Characterization of FGFRL1, a Novel Fibroblast Growth Factor (FGF) Receptor Preferentially Expressed in Skeletal Tissues

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