التفاصيل البيبلوغرافية
| العنوان: |
Ganglioside GD2 in reception and transduction of cell death signal in tumor cells |
| المؤلفون: |
Doronin, Igor I, Vishnyakova, Polina A, Kholodenko, Irina V, Ponomarev, Eugene D, Ryazantsev, Dmitry Y, Molotkovskaya, Irina M, Kholodenko, Roman V |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
GD2, Anti-GD2 mAbs, Cytotoxicity, Cell death, Tumor-associated gangliosides |
| الوصف: |
Background Ganglioside GD2 is expressed on plasma membranes of various types of malignant cells. One of the most promising approaches for cancer immunotherapy is the treatment with monoclonal antibodies recognizing tumor-associated markers such as ganglioside GD2. It is considered that major mechanisms of anticancer activity of anti-GD2 antibodies are complement-dependent cytotoxicity and/or antibody-mediated cellular cytotoxicity. At the same time, several studies suggested that anti-GD2 antibodies are capable of direct induction of cell death of number of tumor cell lines, but it has not been investigated in details. In this study we investigated the functional role of ganglioside GD2 in the induction of cell death of multiple tumor cell lines by using GD2-specific monoclonal antibodies. Methods Expression of GD2 on different tumor cell lines was analyzed by flow cytometry using anti-GD2 antibodies. By using HPTLC followed by densitometric analysis we measured the amount of ganglioside GD2 in total ganglioside fractions isolated from tumor cell lines. An MTT assay was performed to assess viability of GD2-positive and -negative tumor cell lines treated with anti-GD2 mAbs. Cross-reactivity of anti-GD2 mAbs with other gangliosides or other surface molecules was investigated by ELISA and flow cytometry. Inhibition of GD2 expression was achieved by using of inhibitor for ganglioside synthesis PDMP and/or siRNA for GM2/GD2 and GD3 synthases. Results Anti-GD2 mAbs effectively induced non-classical cell death that combined features of both apoptosis and necrosis in GD2-positive tumor cells and did not affect GD2-negative tumors. Anti-GD2 mAbs directly induced cell death, which included alteration of mitochondrial membrane potential, induction of apoptotic volume decrease and cell membrane permeability. This cytotoxic effect was mediated exclusively by specific binding of anti-GD2 antibodies with ganglioside GD2 but not with other molecules. Moreover, the level of GD2 expression correlated with susceptibility ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
http://www.biomedcentral.com/1471-2407/14/295Test |
| الإتاحة: |
http://www.biomedcentral.com/1471-2407/14/295Test |
| حقوق: |
Copyright 2014 Doronin et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.882709E2 |
| قاعدة البيانات: |
BASE |
