Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

被引:49
作者
Mineo, JF
Bordron, A
Quintin-Roué, I
Loisel, S
Ster, KL
Buhé, V
Lagarde, N
Berthou, C
机构
[1] Univ Med Sch Hosp Brest, Dept Neurosurg, F-29609 Brest, France
[2] Univ Med Sch Hosp Brest, Hematol Lab, F-29609 Brest, France
[3] Univ Med Sch Hosp Brest, Lab Pathoanat, F-29609 Brest, France
关键词
glioblastoma; monoclonal antibody; HER2/neu; apoptosis; cytotoxicity;
D O I
10.1038/sj.bjc.6602089
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Glioblastoma multiforme (GBM) remains the most devastating primary tumour in neuro-oncology. Targeting of the human epithelial receptor type 2 (HER2)-neu receptor by specific antibodies is a recent well-established therapy for breast tumours. Human epithelial receptor type 2/neu is a transmembrane tyrosine/kinase receptor that appears to be important for the regulation of cancer growth. Human epithelial receptor type 2/neu is not expressed in the adult central nervous system, but its expression increases with the degree of astrocytoma anaplasia. The specificity of HER2/neu for tumoral astrocytomas leads us to study in vitro treatment of GBM with anti-HER2/neu antibody. We used human GBM cell lines expressing HER2/neu (A172 express HER2/neu more than U251MG) or not (U87MG) and monoclonal humanised antibody against HER2/neu ( Herceptin(R)). Human epithelial receptor type 2/neu expression was measured by immunohistochemistry and flow cytometry. Direct antibody effect, complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity were evaluated by different cytometric assays. We have shown, for the first time, the ability of anti-HER2/neu antibodies to induce apoptosis and cellular-dependent cytotoxicity of HER2/neu-expressing GBM cell lines. The results decreased from A172 to U251 and were negative for U87MG, in accordance with the decreasing density of HER2/neu receptors.
引用
收藏
页码:1195 / 1199
页数:5
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