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Ana Vanesa Torbidoni, Alejandra Scursoni, Sandra Camarero, Claudia Sampor, Guillermo Chantada, Maria T. de Davila; Expression Of N-glycolyl Gm3 In Retinoblastoma, A Promising Candidate For Targeted Therapies. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6883.
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The identification of molecules expressed selectively on the surface of retinoblastoma cells, would allow applying targeted therapies to reach almost exclusively tumor tissue. Gangliosides are potential antigens for cancer targeted therapy, but they are expressed in normal cells. Humans lack the enzyme to synthesize N-Glycolyl GM3 ganglioside (NGcGM3) which is not expressed in human normal tissues. NGcGM3 has been detected in other pediatric neuroectodermic tumors. We sought to characterize the expression of the NGcGM3 in retinoblastoma cell lines and in retinoblastoma tumor samples.
We studied WERI-Rb1 and Y79 cell lines and paraffin embedded tumors from 20 children with retinoblastoma. Fourteen had unilateral disease, 5 of them with extraocular dissemination. The others six had bilateral retinoblastoma. A bone marrow from a metastatic retinoblastoma was also studied. A retinoblastoma free eye was used as control. The 14F7 antibody (provided by Center of Molecular Immunology, La Habana, Cuba) recognizes NGcGM3. Cell lines were fixed and incubated with 14F7, washed and incubated with secondary antibody with FITC. Sections of tumors were incubated with 14F7 and then with peroxidase conjugated secondary antibodies and developed with 3,3'-diaminobenzidine. NGcGM3 expression was evaluated analyzing the percentage of tumour positive cells and the staining intensity.
Both retinoblastoma cell lines showed immunoreactivity to NGcGM3 but WERI-Rb1 presented higher levels of expression than Y79. All the tumors studied showed strong immunoreactivity to NGcGM3, in either intraocular or extraocular sites including those cases with optic nerve or extrascleral invasion. In children that underwent bilateral enucleation we could evaluate NGcGM3 before and after chemotherapy. The expression of NGcGM3 persisted unaltered after chemotherapy. Normal eye and normal retina of affected eyes were completely negative, confirming the absence of this molecule in normal human tissues. In metastatic sites high levels of NGcGM3 were observed in retinoblastoma cells.
Our results indicate that NGc-GM3 is highly expressed in retinoblastoma tumor and it is absent from control eye. Its expression did not decrease after chemotherapy and is present in retinoblastoma cells in metastatic sites. Our results highlight the possibility of using antibodies against this molecule as targeted therapy.
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