Evidence for CEA release from human colon cancer cells by an endogenous GPI-PLD enzyme

Naghibalhossaini, Fakhraddin; Ebadi, Padideh

doi:10.1016/j.canlet.2005.03.028

Cited by 91 publications

(40 citation statements)

References 31 publications

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“…In contrast, it is partially impaired when 1,10 PNT is added to the cell culture medium. This first observation, together with previous studies reporting the involvement of the GPI-PLD1 protease in the release process of GPIanchored membrane receptors (34,35), prompted us to examine the expression of this enzyme in PB-NK lymphocytes. The presence of mRNA transcripts corresponding to the GPI-PLD1 known variant 1 and 2 (32) was first assessed by RT-PCR.…”

Section: Membrane-bound Cd160 Receptor Is Cleaved Through a Metalloprmentioning

confidence: 90%

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A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

Giustiniani

Marie‐Cardine

Bensussan

2007

The Journal of Immunology

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CD160 is a GPI-anchored lymphocyte surface receptor in which expression is mostly restricted to the highly cytotoxic CD56dimCD16+ peripheral blood NK subset. We previously reported that MHC class I (MHC-I) molecules bind to CD160 receptors on circulating NK lymphocytes and that this interaction triggers their cytotoxic activity and cytokine production. We also observed that CD160 surface expression on NK cells is down-modulated upon activation with PMA or IL-2. In this study, we further report that short-time incubation of NK lymphocytes with IL-15 converts the membrane-bound CD160 to a soluble form through a proteolytic cleavage involving a metalloprotease. Thus, CD160 is no longer detected at the cell surface, but can be immunoprecipitated from the NK cell culture medium. Interestingly, CD160 transcript remains highly expressed during the process of protein shedding. In addition, we demonstrate that CD160 mRNA synthesis can be induced in CD56bright separated lymphocytes following exposure to IL-15. By producing a Flag-tagged soluble CD160 protein, we establish that its binding to MHC-I molecules results in the inhibition of the cytotoxic CD8+ T lymphocyte activity and of the CD160-mediated NK cell cytotoxicity. Thus, we show that activated NK lymphocytes release a soluble form of CD160 that functionally impairs the MHC-I-specific cytotoxic CD8+ T lymphocyte responsiveness.

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Section: Membrane-bound Cd160 Receptor Is Cleaved Through a Metalloprmentioning

confidence: 90%

“…Thus, it has been shown that the GPImembrane anchored carcinoembryonic Ag is cleaved from the human colorectal tumor cell line LS180 by a mechanism involving the GPI-PLD protein (35). Two human GPI-specific PLD cDNA have been cloned, corresponding to two protein variants (32).…”

Section: Discussionmentioning

confidence: 99%

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

Giustiniani

Marie‐Cardine

Bensussan

2007

The Journal of Immunology

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“…61 However, GPI anchored proteins; e.g., folate transporter, urokinase receptor and carcinoembryonic antigen are shed from tumor cells due the usually high expression of GPI-specific phospholipase D in tumor cells. [62][63][64][65] In conclusion we have generated three novel human type II transmembrane SA based proteins that were designed for the expression of unique non-mammalian domains at the cell surface of mammalian cells. Thus, cells expressing a marker of choice can be longitudinally tracked in vivo and in tissue samples.…”

Section: Discussionmentioning

confidence: 99%

Development of novel chimeric transmembrane proteins for multimodality imaging of cancer cells

Winnard¹,

Kluth²,

Kato³

et al. 2007

Cancer Biology & Therapy

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Tracking the migration of cancer cells is essential to understanding the metastatic process. In order to facilitate the tracking of metastatic progression, we have generated transgenic cancer cell lines that express novel chimeric proteins composed of truncated human type II transmembrane proteins fused in-frame to a red fluorescence protein. These chimeric proteins have been engineered to display the fluorescence domain on the surface of cells. The three novel chimeric proteins exhibited high transient expression in several cancer cell lines. Membrane expression was well characterized in MCF-7 cell lines that stably express the chimeric proteins. Indirect immunocytochemistry of non-premeablized cells demonstrated co-localization of endogenous red and green fluorescence labeled secondary antibody bound on the cell surfaces. Immunoblots of total protein prepared from membrane, cytosolic and nuclear fractions indicated that the chimeric proteins were mainly associated with the membrane fraction. Further evidence of the membrane expression of these proteins was confirmed by confocal microscopy. Moreover, the chimeric protein was detected on the cell surface by T2-weighted magnetic resonance imaging using anti-red fluorescence protein antibody and superparamagnetic iron oxide particles in vitro and by optical imaging in vivo. The development of this non-mammalian cell surface marker, that can be detected by multi-modality imaging, will find utility in non-invasive longitudinal tracking of biological processes including metastatic progression, solid tumor treatment regimes and the fate of cells used in cell therapies such as islet or stem cells.

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“…Some studies have focused on the inactivation of these enzymes in a range of malignancies. Drugs like pegylated arginine deiminase/ADI-PEG20 (Polaris Group) (Als inhibitor) [47], xanthohumol (Dio3 inhibitor) [48], 1,10-phenanthroline (Gpld1 inhibitor) [49], compounds 54, 66, and 67 (inhibitors of Hsd3b5) [50], and alpha-difluoromethylornithine (Odc1 inhibitor) [51] have already been reported to act as sensitizing anticancer agents. Deregulation of Asah1, an acid ceramidase, and Nmnat2, a nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme, has been involved in a variety of neurodiseases and/or cancers [52,53].…”

Section: Enzymes In Anabolic and Catabolic Chemical Reactionsmentioning

confidence: 99%

Drug target identification at the crossroad of neuronal apoptosis and survival

Maino

Paparone

Severini

et al. 2017

Expert Opinion on Drug Discovery

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Introduction: Inappropriate activation of apoptosis may contribute to neurodegeneration, a multifaceted process that results in various chronic disorders, including Alzheimer's and Parkinson's diseases. Several in vitro and in vivo studies demonstrated that neuronal apoptosis is a multi-pathway cell-death program that requires RNA synthesis. Thus, transcriptionally activated genes whose products induce cell death can be triggered by different stimuli and antagonized by neurotrophic factors. Systems biology is now unveiling the series of intracellular signaling pathways and key drug targets at the intersection of neuronal apoptosis and survival. Areas covered: This review introduces a genomic approach that can be used to elucidate the systems biology of neuronal apoptosis and survival, and to rationally select drug targets, no longer oriented to emulate the action of growth factors at the membrane receptor level, but rather to modulate their downstream signals. Expert opinion: The advent of genomics is offering an unprecedented opportunity to explore how the delicate balance between apoptosis and survival-inducing signals triggers a transcriptional program. Characterization of this program can be useful to identify potential pharmacological targets for existing drugs. Such knowledge might pave the way towards an innovative pharmacology. ARTICLE HISTORY

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Evidence for CEA release from human colon cancer cells by an endogenous GPI-PLD enzyme

Cited by 91 publications

References 31 publications

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

Development of novel chimeric transmembrane proteins for multimodality imaging of cancer cells

Drug target identification at the crossroad of neuronal apoptosis and survival

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