Linked Life Data

12615972

Source:http://linkedlifedata.com/resource/pubmed/id/12615972

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 7
pubmed:dateCreated
2003-3-4
pubmed:abstractText
CA125 is an ovarian cancer antigen whose recently elucidated primary structure suggests that CA125 is a giant mucin-like glycoprotein present on the cell surface of tumor cells. Here, we establish a functional link between CA125 and beta-galactoside-binding, cell-surface lectins, which are components of the extracellular matrix implicated in the regulation of cell adhesion, apoptosis, cell proliferation and tumor progression. On the basis of mass spectrometry and immunological analyses, we find that CA125 is a counter receptor for galectin-1, as both soluble and membrane-associated fragments of CA125 derived from HeLa cell lysates are shown to bind specifically to human galectin-1 with high efficiency. This interaction is demonstrated (1) to depend on beta-galactose-terminated, O-linked oligosaccharide chains of CA125, (2) to be preferential for galectin-1 versus galectin-3 and (3) to be regulated by the cellular background in which CA125 is expressed. Despite lacking a conventional signal peptide, a CA125 C-terminal fragment of 1148 amino acids, representing less than 10% of the full-length protein, retains the ability to integrate into secretory membranes such as the endoplasmic reticulum (ER) and the Golgi, and is targeted to the plasma membrane by conventional secretory transport. As demonstrated by a novel assay that reconstitutes non-conventional secretion of galectin-1 based on fluorescence-activated cell sorting (FACS), we find that tumor-derived HeLa cells expressing endogenous CA125 present more than ten times as much galectin-1 on their surface compared with non-tumor-derived, CA125-deficient CHO cells. Intriguingly, both the galectin-1 expression level and the cell-surface binding capacity for galectin-1 are shown to be similar in CHO and HeLa cells, suggesting that CA125 might be a factor involved in the regulation of galectin-1 export to the cell surface.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1305-18
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12615972-Amino Acid Sequence, pubmed-meshheading:12615972-Animals, pubmed-meshheading:12615972-Antigens, Surface, pubmed-meshheading:12615972-Binding Sites, pubmed-meshheading:12615972-CA-125 Antigen, pubmed-meshheading:12615972-CHO Cells, pubmed-meshheading:12615972-Cell Membrane, pubmed-meshheading:12615972-Cricetinae, pubmed-meshheading:12615972-Galectin 1, pubmed-meshheading:12615972-Galectin 3, pubmed-meshheading:12615972-HeLa Cells, pubmed-meshheading:12615972-Humans, pubmed-meshheading:12615972-Neoplasms, pubmed-meshheading:12615972-Oligosaccharides, Branched-Chain, pubmed-meshheading:12615972-Peptide Fragments, pubmed-meshheading:12615972-Protein Binding, pubmed-meshheading:12615972-Protein Structure, Tertiary, pubmed-meshheading:12615972-Protein Transport, pubmed-meshheading:12615972-Receptors, Cell Surface
pubmed:year
2003
pubmed:articleTitle
The cancer antigen CA125 represents a novel counter receptor for galectin-1.
pubmed:affiliation
Biochemie-Zentrum Heidelberg , Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't