A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells

Günthert, Ursula; Hofmann, Martin; Rudy, Wolfgang; Reber, Simone; Zöller, Margot; Haussmann, Irmgard U.; Matzku, S.; Wenzel, Achim; Ponta, Helmut; Herrlich, Peter

doi:10.1016/0092-8674(91)90403-l

Cited by 1,553 publications

(989 citation statements)

References 44 publications

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“…CD44 can be altered by differential splicing of at least 10 variable exons encoding a segment of the extracellular domain, termed exons v1-v10, and by cell type-specific glycosylation [79]. CD44 has been shown to mediate cell-cell and cell-ECM interactions [80,81], augment tumor cell motility on hyaluronan-coated substrates [81,82], costimulate lymphocyte activation and tissue infiltration [83], and promote growth and metastasis of some tumor types [84,85]. Although GAG chains associated with some CD44 isoforms can also bind a subset of heparin-binding growth factors, cytokines, and ECM proteins such as fibronectin, most of the functions ascribed to CD44 can be attributed to its ability to bind to and internalize hyaluronan [38,86].…”

Section: Versican Interaction With Cd44mentioning

confidence: 99%

The interaction of versican with its binding partners

et al. 2005

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Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix (ECM). Versican, like other members of its family, has unique N-and C-terminal globular regions, each with multiple motifs. A large glycosaminoglycan-binding region lies between them. This review will begin by outlining these structures, in the context of ECM proteoglycans. The diverse binding partners afforded to versican by virtue of its modular design will then be examined. These include ECM components, such as hyaluronan, type I collagen, tenascin-R, fibulin-1, and -2, fibrillin-1, fibronectin, P-and L-selectins, and chemokines. Versican also binds to the cell surface proteins CD44, integrin β1, epidermal growth factor receptor, and P-selectin glycoprotein ligand-1. These multiple interactors play important roles in cell behaviour, and the roles of versican in modulating such processes are discussed.

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Section: Versican Interaction With Cd44mentioning

confidence: 99%

The interaction of versican with its binding partners

et al. 2005

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“…All of the CD44 variants (CD44v) contain insertions of various combinations of variant exons (1-10) located between exons 5 and 16 of the CD44 gene (Screaton et al, 1992(Screaton et al, , 1993. In contrast to merlin, which displays tumor-suppressor activity, CD44 promotes tumor invasion and metastasis (Gunthert et al, 1991;Sherman et al, 1994;Lamb et al, 1997;Yu et al, 1997;Stamenkovic, 1999, 2000).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin

Bai

et al. 2006

Oncogene

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Mutation or loss of expression of merlin is responsible for neurofibromatosis type 2 (NF2), which is characterized by the development of schwannomas and other tumors of the nervous system. Like the ERM (ezrin-radixin-moesin) proteins, merlin interacts with CD44, a cell-surface receptor for hyaluronan (HA) that promotes tumorigenesis. However, the relationship between merlin and CD44 and the mechanism by which merlin exerts its tumorsuppressor function have not been elucidated. In the present study, we show that increased expression of wildtype merlin in Tr6BC1 schwannoma cells inhibits HA binding to CD44. Furthermore, we demonstrate that the residues required for this inhibitory effect and the interaction between CD44 and merlin lie within the first 50 amino acids of merlin. Overexpression of merlin inhibited subcutaneous growth of Tr6BC1 cells in immunocompromised Rag1 mice. In contrast, knocking down expression of endogenous merlin promoted tumor cell growth, as did overexpression of a merlin deletion mutant (merlinDel-1) that lacks the first 50 amino acids but not of other NH 2 -terminal deletion mutants. Together, our results demonstrate that inhibition of the CD44-HA interaction contributes to the tumor-suppressor function of merlin, and they suggest that merlin inhibits tumor growth, at least in part, by negatively regulating CD44 function.

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“…Since it was discovered that the splice variant CD44v4-7 is involved in metastasis of tumor cells, 11 several studies have addressed the relevance of CD44 variant isoforms as diagnostic and prognostic markers for human tumors (reviewed by Herrlich et al 9 and Gü nthert et al 12 ). In multiple myeloma, CD44v9 expression in the absence of CD44v10 on bone marrow plasma cells is associated with a progressive phase of disease, 13 while CD44v9 expression on bone marrow biopsies of myeloma patients is correlated with an adverse prognosis.…”

Section: Introductionmentioning

confidence: 99%

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

et al. 2005

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There is growing evidence that one of the central common characteristics of tumor and inflammatory cells is their resistance to programmed cell death. This feature results in the accumulation of harmful cells, which are mostly refractory to Fas (FAS, APO-1)-mediated apoptosis. A molecule found on these cells is the transmembrane receptor CD44 with its variant isoforms (CD44v). The establishment of transfectants expressing different CD44v isoforms allowed us to demonstrate that the CD44v6 and CD44v9 isoforms exhibit an antiapoptotic effect and can block Fas-mediated apoptosis. Moreover, we observed that CD44v6 and CD44v9 colocalize and interact with Fas. Importantly, an anti-CD44v6 antibody can abolish the antiapoptotic effect of CD44v6. These results are the first to show that CD44v isoforms interfere with Fas signaling. Our findings improve the understanding of the pathogenesis of cancer and autoimmunity and open new strategies to treat such disorders.

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A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells

Cited by 1,553 publications

References 44 publications

The interaction of versican with its binding partners

The interaction of versican with its binding partners

Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

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