ECSA/DPPA2 is an embryo-cancer antigen that Is coexpressed with cancer-testis antigens in non-small cell lung cancer Journal Article
| Authors: | John, T.; Caballero, O. L.; Svobodová, S. J.; Kong, A.; Chua, R.; Browning, J.; Fortunato, S.; Deb, S.; Hsu, M.; Gedye, C. A.; Davis, I. D.; Altorki, N.; Simpson, A. J.; Chen, Y. T.; Monk, M.; Cebon, J. S. |
| Article Title: | ECSA/DPPA2 is an embryo-cancer antigen that Is coexpressed with cancer-testis antigens in non-small cell lung cancer |
| Abstract: | Purpose: Cancer cells recapitulate many behaviors of pluripotent embryonic cells such as unlimited proliferation, and the capacity to self-renew and to migrate. Embryo-cancer sequence A (ECSA), later named developmental pluripotency associated-2 (DPPA2), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/ DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy. Experimental Design: ECSA/DPPA2 expression was examined in a panel of normal and tumor tissue by reverse transcription PCR, quantitative real-time PCR, and immunohistochemistry. A panel of 110 non - small cell lung cancers (NSCLC) were further investigated for the presence of ECSA/DPPA2 transcripts and several cancer testis antigens (CTA). Sera from 104 patients were analyzed for spontaneous ECSA/DPPA2 antibody production by ELISA and Western blot. Results: ECSA/DPPA 2 transcripts were limited to normal testis, placenta, bone marrow, thymus, and kidney but expressed in a variety of tumors most notably in 30% of NSCLC. Enrichment for CTAs in fCS4/DPiR42-positive NSCLC was observed. Immunohistochemistry confirmed nuclear and cytoplasmic localization in subpopulations of cells with coexpression of the CTA MAGE-A3. Antibodies to recombinant ECSA/DPPA2 protein were detected in the sera of 4 of 104 patients with NSCLC but not in healthy controls. Conclusions: The restricted expression in normal tissues, expression in tumors with coexpression of CTAs, and spontaneous immunogenicity indicate that ECSA/DPPA 2 is a promising target for antigen-specific immunotherapy in NSCLC. © 2008 American Association for Cancer Research. |
| Keywords: | immunohistochemistry; human tissue; unclassified drug; protein localization; antigen expression; metabolism; reverse transcription polymerase chain reaction; gene expression; gene expression profiling; nuclear protein; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; tumor antigen; enzyme linked immunosorbent assay; nuclear proteins; lung tumor; blotting, western; biosynthesis; antigens, neoplasm; reverse transcriptase polymerase chain reaction; cancer testis antigen; western blotting; cytoplasm; cell nucleus; enzyme-linked immunosorbent assay; antibody production; embryo cancer sequence a antigen; fetal antigen; dppa2 protein, human |
| Journal Title: | Clinical Cancer Research |
| Volume: | 14 |
| Issue: | 11 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-06-01 |
| Start Page: | 3291 |
| End Page: | 3298 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-07-1322 |
| PUBMED: | 18519755 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
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