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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1998-1-8
|
| pubmed:abstractText |
Amplification and over-expression of the HER-2/neu proto-oncogene are associated with poor prognosis in women with both node-positive and node-negative breast cancer. Therefore, the encoded surface glycoprotein represents an attractive target for cancer immunotherapies. Furthermore, the extracellular domain of HER-2/neu is released from the cell surface by proteolytic cleavage. In the present experiments, we investigated the potential biologic effects of soluble HER-2/neu with particular emphasis on its interaction with anti-HER-2/neu antibodies. A monoclonal antibody specific for the extracellular domain of HER-2/neu dose dependently inhibited the proliferation of highly HER-2/neu-expressing SK-BR-3 and BT-474 breast cancer cells but had no effect on the proliferation of weakly to moderately HER-2/neu-expressing MCF-7, HBL-100 and ZR-75-1 breast cells. Addition of SK-BR-3 or BT-474 cell supernatants with high concentrations of soluble HER-2/neu led to a neutralization of anti-HER-2/neu antibody-mediated inhibition of proliferation due to a binding of soluble HER-2/neu by the antibody, which could be demonstrated by immunoprecipitation. Furthermore, the ability of anti-HER-2/neu antibodies to mediate antibody-dependent cellular cytotoxicity (ADCC) by lymphokine-activated killer cells was assessed. Cytolysis of SK-BR-3 tumor cells was increased significantly in the presence of anti-HER-2/neu antibodies. Similar to the proliferation inhibition, ADCC was neutralized by addition of soluble HER-2/neu-containing supernatants. Our data suggest that tumors rich in HER-2/neu might thus escape certain steps of immunologic control by neutralizing biologic activities of anti HER-2/neu antibodies due to the presence of soluble HER-2/neu.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0020-7136
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
10
|
| pubmed:volume |
73
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
875-9
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9399669-Antibodies, Monoclonal,
pubmed-meshheading:9399669-Antibody-Dependent Cell Cytotoxicity,
pubmed-meshheading:9399669-Breast,
pubmed-meshheading:9399669-Breast Neoplasms,
pubmed-meshheading:9399669-Cell Division,
pubmed-meshheading:9399669-Cells, Cultured,
pubmed-meshheading:9399669-Culture Media, Conditioned,
pubmed-meshheading:9399669-Female,
pubmed-meshheading:9399669-Humans,
pubmed-meshheading:9399669-Immunotherapy,
pubmed-meshheading:9399669-Receptor, erbB-2,
pubmed-meshheading:9399669-Solubility,
pubmed-meshheading:9399669-Tumor Cells, Cultured
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Soluble HER-2/neu neutralizes biologic effects of anti-HER-2/neu antibody on breast cancer cells in vitro.
|
| pubmed:affiliation |
Clinical Division of Oncology, University Hospital, Vienna, Austria.
|
| pubmed:publicationType |
Journal Article
|