Primary human ovarian epithelial cancer cells broadly express HER2 at immunologically-detectable levels.

Détails

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Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_8DF38EB47D0C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Primary human ovarian epithelial cancer cells broadly express HER2 at immunologically-detectable levels.
Périodique
Plos One
Auteur⸱e⸱s
Lanitis E., Dangaj D., Hagemann I.S., Song D.G., Best A., Sandaltzopoulos R., Coukos G., Powell D.J.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2012
Volume
7
Numéro
11
Pages
e49829
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
The breadth of HER2 expression by primary human ovarian cancers remains controversial, which questions its suitability as a universal antigen in this malignancy. To address these issues, we performed extensive HER2 expression analysis on a wide panel of primary tumors as well as established and short-term human ovarian cancer cell lines. Conventional immunohistochemical (IHC) analysis of multiple tumor sites in 50 cases of high-grade ovarian serous carcinomas revealed HER2 overexpression in 29% of evaluated sites. However, more sensitive detection methods including flow cytometry, western blot analysis and q-PCR revealed HER2 expression in all fresh tumor cells derived from primary ascites or solid tumors as well as all established and short-term cultured cancer cell lines. Cancer cells generally expressed HER2 at higher levels than that found in normal ovarian surface epithelial (OSE) cells. Accordingly, genetically-engineered human T cells expressing an HER2-specific chimeric antigen receptor (CAR) recognized and reacted against all established or primary ovarian cancer cells tested with minimal or no reactivity against normal OSE cells. In conclusion, all human ovarian cancers express immunologically-detectable levels of HER2, indicating that IHC measurement underestimates the true frequency of HER2-expressing ovarian cancers and may limit patient access to otherwise clinically meaningful HER2-targeted therapies.
Mots-clé
Cell Line, Tumor, Epithelial Cells/metabolism, Female, Gene Expression, Humans, Immunohistochemistry, Neoplasms, Glandular and Epithelial/genetics, Neoplasms, Glandular and Epithelial/metabolism, Ovarian Neoplasms/genetics, Ovarian Neoplasms/metabolism, Ovary/cytology, Ovary/metabolism, Receptor, erbB-2/genetics, Receptor, erbB-2/immunology, T-Lymphocytes/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/10/2014 11:43
Dernière modification de la notice
20/08/2019 14:51
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