Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to clarify the role of carcinoembryonic antigen (CEA) in the aggregation of colorectal carcinoma (CRC) cells in malignant effusions. We analysed freshly purified CRC cells from one patient, which expressed CEA (98% positive cells) on the surface and formed huge cell aggregates in the patient's ascites. The carcinoma cells expressed Sialyl Lewis A (82%), Sialyl Lewis X (92%) and the beta 1 integrin subunit (78%) but did not express the pair-ligands for these molecules. Cell aggregation was completely inhibited by anti-CEA mAb. The decreased CEA expression induced by phosphatidylinositol-specific phospholipase C (PI-PLC) treatment led to decreased cell aggregation. We also examined the correlation between the degree of cell aggregation and CEA expression using smears of ascites fluid from 27 patients with colorectal cancer. There was a significant correlation between the degree of cell aggregation and CEA expression by CRC cells. The present study provided the first evidence that CEA molecules mediate the homotypic aggregation of CRC cells in malignant effusions.
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PMID:CEA-mediated homotypic aggregation of human colorectal carcinoma cells in a malignant effusion. 785 Jul 76

Recent studies have shown that, even with a minimal content of carcinoembryonic antigen (CEA), normal human colonic epithelial cells express substantial amounts of CEA mRNA and colonic mucosal fragments cultured in vitro produce CEA quite actively, indicating that CEA should no longer be considered to be of an oncofetal nature. To understand the basis of the usefulness of CEA as a tumor marker, we analyzed the release of CEA, a glycosyl-phosphatidylinositol (GPI)-anchored protein, from colonic epithelial cells, by culturing isolated colonic crypts in collagen gel. The crypts appeared to preserve their morphological and biochemical integrity in the gel for at least 16 hr, and released CEA spontaneously. Three forms of CEA--spontaneously released CEA, CEA liberated with phosphatidylinositol-specific phospholipase C (PI-PLC) and CEA in cell lysates--were indistinguishable on SDS-PAGE. This is in contrast to recombinant CEA spontaneously released from CHO transfectants, which showed a smaller molecular mass than that of PI-PLC-cleaved recombinant CEA. By phase separation using Triton X-114, CEA in the cell lysates of crypts was separated mostly into the detergent phase, while the spontaneously released and the PI-PLC-cleaved CEA were separated into the aqueous phase. When the cells were metabolically labeled with the precursors of the GPI-anchor, 3H-ethanolamine but not 3H-palmitic acid was found in the spontaneously released CEA. These findings suggest that, in contrast to the proteolysis-like release of the recombinant CEA from CHO cells, CEA in normal colonic epithelial cells is released by a non-proteolytic cleavage, which probably occurs through the action of some endogenous phospholipase.
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PMID:Non-proteolytic release of carcinoembryonic antigen from normal human colonic epithelial cells cultured in collagen gel. 801 5

NCC-CO-411, an anti-carcinoembryonic antigen (CEA) monoclonal antibody (MoAb) showed a dose-dependent reactivity with standard CEA, but did not bind to the CEA anchoring with cell membranes. When LS 174T cells, one of the CEA-producing cells, were treated with phosphatidylinositol-specific phospholipase C, NCC-CO-411 MoAb recognized the released CEA containing glycosylphosphatidylinositol as well as the standard CEA. The binding activity of NCC-CO-411 MoAb with CEA was also demonstrated by the immunostaining of the LS 174T colorectal tumor xenograft tissues. The biodistribution study showed that NCC-CO-411 MoAb was mainly taken up by tumor and kidney, while the anti-hCEA MoAb was largely concentrated in liver and spleen rather than in the tumor. These results suggest that NCC-CO-411 MoAb recognizes the released CEA and gives an excellent tumor image in LS 174T tumor-bearing mice.
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PMID:Accumulation of NCC-CO-411 monoclonal antibody in human colorectal adenocarcinoma through binding of the released carcinoembryonic antigen in nude mice. 883 61

By using a retrovirus-derived system we generated derivatives of the human colon adenocarcinoma cell line LS174T (ATCC CL 188) that stably overexpress a full-length cDNA encoding the beta 1 isoform of bovine phosphoinositides-specific phospholipase C (PI-PLC). This was confirmed by the elevated levels of catalytic activity to release phosphoinositides from phosphatidylinositol (PI-PLC) or phosphatidylinositol-bis-phosphate (PIP2-PLC), and the enhanced expressions of messenger RNA and protein. PI-PLC beta 1 overexpresser clones grew to form cell clumps floating in liquid medium, whereas the pMV7-introduced control clones displayed morphologic characteristics that were very similar to those of the parent LS174T cell line. Three individual PI-PLC beta 1 overexpresser cell lines displayed increased doubling time (18.0 h, 21.5 h, and 23.8 h) when compared with 4 individual pMV7-introduced control cell lines (13.1 h, 10.7 h, 12.9 h, and 9.3 h). Anchorage-independent growth ability in soft agar medium was dramatically suppressed by overexpression of PLC beta 1, and the ability of PLC-overproducer clones to form aggregates when cultured in liquid medium was dramatically enhanced when compared with that of pMV7-introduced control clones. Tumorigenicity of PLC beta 1-overproducers was much weaker than that of vector-transduced control clones. The spontaneous release of carcinoembryonic antigen from PLC beta 1-overproducer clones was much higher than that from pMV7 control clones. The ability of PLC beta 1-overproducer clones to form aggregates during suspension culture was much stronger than that of the control clones. These results provide the first evidence that elevated levels of endogenous PI-PLC beta 1 suppress tumor cell growth, but enhance the ability to form cell aggregates and to release carcinoembryonic antigen, an intercellular adhesion molecule.
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PMID:Growth inhibition, enhancement of intercellular adhesion, and increased expression of carcinoembryonic antigen by overexpression of phosphoinositides-specific phospholipase C beta 1 in LS174T human colon adenocarcinoma cell line. 1008 86

Individual Neisseria gonorrhoeae colony opacity-associated (Opa) protein variants can bind up to four different carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) receptors. Most human cells encountered by gonococci express a combination of CEACAM receptors, thereby complicating the elucidation of intracellular signaling pathways triggered by individual receptors. Here, we compare the process of bacterial engulfment by a panel of stably transfected HeLa epithelial cell lines expressing each CEACAM receptor in isolation. CEACAM1 and CEACAM3 each contain proteinaceous transmembrane and cytoplasmic domains; however, the processes of neisserial uptake mediated by these receptors differ with respect to their susceptibilities to both tyrosine kinase inhibitors and the actin microfilament-disrupting agent cytochalasin D. Neisserial uptake mediated by glycosylphosphatidylinositol (GPI)-anchored CEACAM5 and CEACAM6 was not significantly affected by any of a broad spectrum of inhibitors tested. However, cleavage of the GPI anchor by phosphatidylinositol-specific phospholipase C reduced bacterial uptake by HeLa cells expressing CEACAM5, consistent with a single zipper-like mechanism of uptake mediated by this receptor. Regardless of the CEACAM receptor expressed, internalized gonococci were effectively killed by a microtubule-dependent process that required acidification of the bacterium-containing phagosome. Given the phase-variable nature of neisserial Opa proteins, these results indicate that the mechanism of bacterial engulfment and the cellular response to gonococcal infection depend on both the receptor specificities of the neisserial Opa protein variants expressed and the spectrum of CEACAM receptors present on target cells, each of which determines the combination of receptors ultimately engaged.
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PMID:Engulfment of Neisseria gonorrhoeae: revealing distinct processes of bacterial entry by individual carcinoembryonic antigen-related cellular adhesion molecule family receptors. 1510 84

Tumor necrosis factor-alpha (TNF-alpha) binds to TNF-alpha receptors (TNFR) to produce a hexameric (TNF-alpha)(3)-(TNFR)(3) structure that stimulates apoptosis. We found by using ELISA that TNF-alpha binds to the glycosylphosphatidylinositol (GPI) anchor glycans of carcinoembryonic antigen, human placental alkaline phosphatase (hAP), and Tamm-Horsfall glycoprotein. These binding abilities were inhibited by 10(-6)M mannose-6-phosphate. Treatment of hAP with mild acid and phosphatase, which releases the N-acetylglucosamine (GlcNAc) beta1 -->phosphate-->6 residue from the GPI-anchor glycan of hAP, abrogated the binding of TNF-alpha to hAP. Thus, TNF-alpha binds to the GlcNAcbeta1-->phosphate-->6Man residue in GPI-anchor glycans. To investigate whether the carbohydrate-binding ability of TNF-alpha is related to its physiological functions, human lymphoma U937 cells were used. TNF-alpha stimulates U937 cell apoptosis in a dose-dependent manner and the presence of mannose-6-phosphate inhibited this. TNF-alpha-dependent tyrosine phosphorylation of several proteins in U937 cells was also diminished by mannose-6-phosphate. Phosphatidylinositol-specific phospholipase C-pretreatment also inhibited this tyrosine phosphorylation. These data suggest that TNF-alpha stimulates U937 cell apoptosis by forming a high-affinity nanomeric (TNF-alpha)(3)-(TNFR)(3)-(GPI-anchored glycan)(3) complex. The GPI-anchored glycoprotein involved remains to be identified.
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PMID:Recognition by TNF-alpha of the GPI-anchor glycan induces apoptosis of U937 cells. 1515 80


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