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Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin

CD44 is a family of glycoproteins involved in cell-cell and cell-matrix interactions. In addition to the major 90-kD form present on most hematopoietic cells, larger 140-230 kD forms are found on keratinocytes and carcinoma cell lines. These bigger isoforms of CD44 arise by alternative splicing that...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1993
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119652/
https://www.ncbi.nlm.nih.gov/pubmed/8320265
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description CD44 is a family of glycoproteins involved in cell-cell and cell-matrix interactions. In addition to the major 90-kD form present on most hematopoietic cells, larger 140-230 kD forms are found on keratinocytes and carcinoma cell lines. These bigger isoforms of CD44 arise by alternative splicing that results in insertion of one or more of the "variant" exons into the extracellular part of the 90-kD constant form of the molecule. In rat, v6 (variant exon v6) containing form of CD44 confers metastatic potential to carcinoma cells, and therefore, it is of interest to study the distribution of this isoform in humans. We raised antibodies against a synthetic peptide containing a sequence encoded by the exon v6. A mAb thus obtained (designated Var3.1) strongly reacted with the plasma membranes of squamous cells in upper layers of skin and tonsil surface epithelia. Weaker staining was seen in germinal centers, vascular endothelia and enterocytes. Exon v6 containing forms of CD44 (CD44v6) were absent from tissue leukocytes and connective tissue components. In comparison, Hermes-3 epitope (on the constant part) containing forms of CD44 were preferentially localized in basal layers of epithelia, present on the surface on most leukocytes and connective tissue cells, and undetectable on the luminal surface of high endothelial venules. In benign neoplasms, epithelial cells stained with mAb Var3.1 like in normal tissues. In contrast, immunostaining of 30 squamous carcinoma specimens (both primary and metastatic lesions) revealed that malignant transformation resulted in downregulation or disappearance of Var3.1 epitope, but in majority of cases, not in diminished synthesis of the Hermes-3 epitope. Biochemical analyses showed that mAb Var3.1 recognized two major forms of CD44 (220 and 300 kD). In conclusion, epitopes on exon v6 and constant part of CD44 are differentially synthesized and regulated during normal and malignant growth of cells in man.
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spelling pubmed-21196522008-05-01 Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin J Cell Biol Articles CD44 is a family of glycoproteins involved in cell-cell and cell-matrix interactions. In addition to the major 90-kD form present on most hematopoietic cells, larger 140-230 kD forms are found on keratinocytes and carcinoma cell lines. These bigger isoforms of CD44 arise by alternative splicing that results in insertion of one or more of the "variant" exons into the extracellular part of the 90-kD constant form of the molecule. In rat, v6 (variant exon v6) containing form of CD44 confers metastatic potential to carcinoma cells, and therefore, it is of interest to study the distribution of this isoform in humans. We raised antibodies against a synthetic peptide containing a sequence encoded by the exon v6. A mAb thus obtained (designated Var3.1) strongly reacted with the plasma membranes of squamous cells in upper layers of skin and tonsil surface epithelia. Weaker staining was seen in germinal centers, vascular endothelia and enterocytes. Exon v6 containing forms of CD44 (CD44v6) were absent from tissue leukocytes and connective tissue components. In comparison, Hermes-3 epitope (on the constant part) containing forms of CD44 were preferentially localized in basal layers of epithelia, present on the surface on most leukocytes and connective tissue cells, and undetectable on the luminal surface of high endothelial venules. In benign neoplasms, epithelial cells stained with mAb Var3.1 like in normal tissues. In contrast, immunostaining of 30 squamous carcinoma specimens (both primary and metastatic lesions) revealed that malignant transformation resulted in downregulation or disappearance of Var3.1 epitope, but in majority of cases, not in diminished synthesis of the Hermes-3 epitope. Biochemical analyses showed that mAb Var3.1 recognized two major forms of CD44 (220 and 300 kD). In conclusion, epitopes on exon v6 and constant part of CD44 are differentially synthesized and regulated during normal and malignant growth of cells in man. The Rockefeller University Press 1993-07-02 /pmc/articles/PMC2119652/ /pubmed/8320265 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin
title Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin
title_full Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin
title_fullStr Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin
title_full_unstemmed Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin
title_short Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin
title_sort regulated expression of exon v6 containing isoforms of cd44 in man: downregulation during malignant transformation of tumors of squamocellular origin
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119652/
https://www.ncbi.nlm.nih.gov/pubmed/8320265