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

Mineo JF, Bordron A, Quintin-Roué I, Loisel S, Ster KL, Buhé V, Lagarde N, Berthou C - Br. J. Cancer (2004)

Bottom Line: 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).Human epithelial receptor type 2/neu expression was measured by immunohistochemistry and flow cytometry.The results decreased from A172 to U251 and were negative for U87MG, in accordance with the decreasing density of HER2/neu receptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, University Medical School Hospital of Brest, BP 824, F29609 Brest Cedex, France. jfmineo@hotmail.com

ABSTRACT
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). 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.

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Increasing apoptosis in glioblastomas cell lines expressing HER2/neu: Cells were incubated for 24 h with different concentrations of Herceptin®.
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fig2: Increasing apoptosis in glioblastomas cell lines expressing HER2/neu: Cells were incubated for 24 h with different concentrations of Herceptin®.

Mentions: Apoptosis induction: The A172 cell line expressing HER2/neu undergo apoptosis, following incubation with Herceptin®. Cells were incubated for 24 h with medium (A) or with 25 μg of Herceptin® (B). The cells staining with FITC-conjugated Annexin V and PI. Apoptotic cells were identified as Annexin V positive and PI negative. (C) Time course analysis of PS exposure after incubation of A172 cell line Herceptin® 25 μg ml−1. Only 24 h results are statistically significant (P<0.01).


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

Mineo JF, Bordron A, Quintin-Roué I, Loisel S, Ster KL, Buhé V, Lagarde N, Berthou C - Br. J. Cancer (2004)

Increasing apoptosis in glioblastomas cell lines expressing HER2/neu: Cells were incubated for 24 h with different concentrations of Herceptin®.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747695&req=5

fig2: Increasing apoptosis in glioblastomas cell lines expressing HER2/neu: Cells were incubated for 24 h with different concentrations of Herceptin®.
Mentions: Apoptosis induction: The A172 cell line expressing HER2/neu undergo apoptosis, following incubation with Herceptin®. Cells were incubated for 24 h with medium (A) or with 25 μg of Herceptin® (B). The cells staining with FITC-conjugated Annexin V and PI. Apoptotic cells were identified as Annexin V positive and PI negative. (C) Time course analysis of PS exposure after incubation of A172 cell line Herceptin® 25 μg ml−1. Only 24 h results are statistically significant (P<0.01).

Bottom Line: 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).Human epithelial receptor type 2/neu expression was measured by immunohistochemistry and flow cytometry.The results decreased from A172 to U251 and were negative for U87MG, in accordance with the decreasing density of HER2/neu receptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, University Medical School Hospital of Brest, BP 824, F29609 Brest Cedex, France. jfmineo@hotmail.com

ABSTRACT
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). 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.

Show MeSH
Related in: MedlinePlus