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

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Serval ID
serval:BIB_8DF38EB47D0C
Type
Article: article from journal or magazin.
Collection
Publications
Title
Primary human ovarian epithelial cancer cells broadly express HER2 at immunologically-detectable levels.
Journal
Plos One
Author(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
Publication state
Published
Issued date
2012
Volume
7
Number
11
Pages
e49829
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
14/10/2014 11:43
Last modification date
20/08/2019 14:51
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