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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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CD45 expression on the GBM cell lines and leucocytes: Cells were stained by FITC-conjugated mouse anti-human CD45 for 30 min at 4°C. Flow cytometry allowed us to differentiate the glioblastoma and effector cells.
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fig3: CD45 expression on the GBM cell lines and leucocytes: Cells were stained by FITC-conjugated mouse anti-human CD45 for 30 min at 4°C. Flow cytometry allowed us to differentiate the glioblastoma and effector cells.

Mentions: During ADCC assay establishment, we measured the density of membranous CD45. We observed that this molecule was highly expressed by effector cytotoxic cells. This allowed us to differentiate the two cellular types (GBM and effectors; Figure 3Figure 3


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)

CD45 expression on the GBM cell lines and leucocytes: Cells were stained by FITC-conjugated mouse anti-human CD45 for 30 min at 4°C. Flow cytometry allowed us to differentiate the glioblastoma and effector cells.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: CD45 expression on the GBM cell lines and leucocytes: Cells were stained by FITC-conjugated mouse anti-human CD45 for 30 min at 4°C. Flow cytometry allowed us to differentiate the glioblastoma and effector cells.
Mentions: During ADCC assay establishment, we measured the density of membranous CD45. We observed that this molecule was highly expressed by effector cytotoxic cells. This allowed us to differentiate the two cellular types (GBM and effectors; Figure 3Figure 3

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