Comparative biochemical and immunological studies on gamma-glutamyltransferases from human kidney and renal cell carcinoma applying monoclonal antibodies

Fischer, P.; Scherberich, Jürgen E.; Schoeppe, W.

doi:10.1016/0009-8981(90)90020-s

Cited by 23 publications

(40 citation statements)

References 33 publications

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“…109 established and characterized in our laboratory), and γ-glutamyl transferase (γGT; EC 3.4.13.14): mouse antihuman γGT (antibody was produced by hybridoma No. 138H11 established in our laboratory) [9]. For immunofluorescence studies, we used a Cy3-conjugated goat antimouse IgG + IgM mAb as a secondary antibody (Dianova, Hamburg, Germany).…”

Section: Methodsmentioning

confidence: 99%

Transdifferentiation of Distal but Not Proximal Tubular Epithelial Cells from Human Kidney in Culture

Baer

Tunn

Nunez

et al. 1999

Nephron Exp Nephrol

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Human renal proximal and distal (thick ascending limb and early distal convoluted tubule) epithelial cells have been isolated according to their specific antigen expression. The cells were well characterized by flow cytometry, enzyme cytochemistry and electron microscopy and cultured for up to 3 months. Cultured tubular cells coexpressed cytokeratin and vimentin as intermediate filament proteins. While primary isolated cells, proximal as well as distal, revealed the phenotypic characteristics of their nephron origin, cultured distal cells showed the tendency to dedifferentiate/transdifferentiate. Distal cells lost their characteristic expression of Tamm-Horsfall glycoprotein and started de novo expression of the proximal marker proteins aminopeptidase M, γ-glutamyl transferase and dipeptidyl peptidase IV. The expression of these antigens by distal cells could be shown by flow-cytometric analysis and fluorescence microscopy. Enzyme activity assays revealed the activity of aminopeptidase M, γ-glutamyl transferase and dipeptidyl peptidase IV, but not of the proximal marker enzyme alkaline phosphatase. This antigenic shift could not be prevented in different culture media, and the original phenotype could not be restored. Cultured cells displayed characteristic hormonal stimulation patterns indicative of their proximal and distal origins, as shown by activation of adenylate cyclase by different peptide hormones. These results indicate that distal tubular cells possibly transdifferentiate to a more proximal phenotype in view of loss of the distal marker enzyme Tamm-Horsfall protein and de novo expression of proximal marker enzymes like dipeptidyl peptidase IV and aminopeptidase M.

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Section: Methodsmentioning

confidence: 99%

Transdifferentiation of Distal but Not Proximal Tubular Epithelial Cells from Human Kidney in Culture

Baer

Tunn

Nunez

et al. 1999

Nephron Exp Nephrol

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“…This MAb reacted with all normal as well as RCC yGT isoforms [9,[13][14][15]. However, MAb 138H11 demon strated a different expression pattern of yGT on RCC cells compared to normal kidneys.…”

Section: Introductionmentioning

confidence: 99%

“…The isolation procedure and enzyme assays have been described in detail elsewhere [9,17]. Briefly, freshly frozen human RCC were thawed, homogenized with an omnimixer and digested with bromelain for 3 h at 370 C to solubilize membrane-bound yGT.…”

Section: Isolation O F Ygt From Rccmentioning

confidence: 99%

“…In particular, an isoform of y-glutamyltransferase (yGT) was purified from RCC using concanavalin A (ConA) affinity chromatography. This RCC yGT comprises about 50% of the enzymatic activity found in the tumor tissue in half the RCC patients [9][10][11][12], In contrast, less than 2% of the yGT activity in normal renal tissue bound to ConA. Further biochemical differ ences between those isoforms such as various molecular weights and isoelectric points were demonstrated [9],…”

Section: Introductionmentioning

confidence: 99%

“…There, the 138H11 anti gen was expressed in large amounts on the outer membrane of the tumor cells ( fig. 1) [9,13]. Therefore, when human tumor-bearing kidneys were perfused in an extracorporeal system with radiolabelled MAb 138H11, a specific binding of circulating antibody to the tumor cells was demonstrated ( fig.…”

Section: Introductionmentioning

confidence: 99%

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Hybridomas Reveal Shared Immunodominant Epitopes of γ-Glutamyltransferase Isoforms from Human Kidney and Renal Cell Carcinoma

Fischer

Scherberich²

1996

Tumor Biol

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Metastatic renal cell carcinoma (RCC) is a tumor with a poor prognosis resistant to chemotherapy and irradiation. However, in rare cases, spontaneous regressions of metastases after nephrectomy have been reported that were ascribed to destruction of the tumor by the immune system. In earlier studies, we and others identified the expression of modified antigens in RCC. In particular, a concanavalin A-binding isoform of γ-glutamyltrans-ferase (γGT) comprises about 50% of the enzymatic activity found in the tumor tissue of many RCC patients. The monoclonal antibody 138H11, directed against all human γGT isoforms, revealed a membranous expression of γGT around RCC cells compared to the restricted, apical pattern of renal cells. These data raised the question why the RCC-specific γGT, exposed to the immune system in vivo, is not immunogenic in patients with RCC. To address this question, we generated mouse hybridomas against highly purified human RCC γGT. Although we obtained a large panel of hybridomas that produced antibodies reacting immunohisto-chemically in a γGT-specific manner, all antibodies stained normal kidney γGT as well as RCC γGT. These results suggest that the biochemical features specific for RCC γGT are not necessarily reflected by specific anti-genic determinants that could be differentiated by the immune system of the challenged mice. The lack of immunogenic epitopes different from normal γGT enzyme may offer an explanation why γGT produced by RCC can escape immunological surveillance.

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Monoclonal Antibody 138H11 against Gamma-Glutamyltransferase Provides a Possible Tool for Targeting Calicheamicin θ to Renal Cell Carcinomas

Schmidt

Wrasidlo

Kaufmann

et al. 1998

Advances in Experimental Medicine and Biology

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Comparative biochemical and immunological studies on gamma-glutamyltransferases from human kidney and renal cell carcinoma applying monoclonal antibodies

Cited by 23 publications

References 33 publications

Transdifferentiation of Distal but Not Proximal Tubular Epithelial Cells from Human Kidney in Culture

Transdifferentiation of Distal but Not Proximal Tubular Epithelial Cells from Human Kidney in Culture

Hybridomas Reveal Shared Immunodominant Epitopes of γ-Glutamyltransferase Isoforms from Human Kidney and Renal Cell Carcinoma

Monoclonal Antibody 138H11 against Gamma-Glutamyltransferase Provides a Possible Tool for Targeting Calicheamicin θ to Renal Cell Carcinomas

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Comparative biochemical and immunological studies on gamma-glutamyltransferases from human kidney and renal cell carcinoma applying monoclonal antibodies

Cited by 23 publications

References 33 publications

Transdifferentiation of Distal but Not Proximal Tubular Epithelial Cells from Human Kidney in Culture

Transdifferentiation of Distal but Not Proximal Tubular Epithelial Cells from Human Kidney in Culture

Hybridomas Reveal Shared Immunodominant Epitopes of &gamma;-Glutamyltransferase Isoforms from Human Kidney and Renal Cell Carcinoma

Monoclonal Antibody 138H11 against Gamma-Glutamyltransferase Provides a Possible Tool for Targeting Calicheamicin θ to Renal Cell Carcinomas

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Hybridomas Reveal Shared Immunodominant Epitopes of γ-Glutamyltransferase Isoforms from Human Kidney and Renal Cell Carcinoma