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International Journal of Colorectal Disease

Published in:

01-06-2013 | Original Article

Expression and potential role of apolipoprotein D on the death–survival balance of human colorectal cancer cells under oxidative stress conditions

Authors: Raquel Bajo-Grañeras, Jesús Crespo-Sanjuan, Rosa M. García-Centeno, José Antonio Garrote-Adrados, Gabriel Gutierrez, Manuel García-Tejeiro, Beatriz Aguirre-Gervás, María D. Calvo-Nieves, Rosa Bustamante, Maria D. Ganfornina, Diego Sanchez

Published in: International Journal of Colorectal Disease | Issue 6/2013

Abstract

Purpose

Inverse correlations of apolipoprotein D (ApoD) expression with tumor growth have been shown, therefore proposing ApoD as a good prognostic marker for diverse cancer types, including colorectal cancer (CRC). Besides, ApoD expression is boosted upon oxidative stress (OS) in many pathological situations. This study aims at understanding the role of ApoD in the progression of human CRC.

Methods

Samples of CRC and distant normal tissue (n = 51) were assayed for levels of lipid peroxidation, expression profile of OS-dependent genes, and protein expression. Three single-nucleotide polymorphisms in the ApoD gene were analyzed (n = 139), with no significant associations found. Finally, we assayed the effect of ApoD in proliferation and apoptosis in the CRC HT-29 cell line.

Results

In CRC, lipid peroxides increase while ApoD messenger RNA and protein decrease through tumor progression, with a prominent decrease in stage I. In normal mucosa, ApoD protein is present in lamina propia and enteroendocrine cells. In CRC, ApoD expression is heterogeneous, with low expression in stromal cells commonly associated with high expression in the dysplastic epithelium. ApoD promoter is basally methylated in HT-29 cells but retains the ability to respond to OS. Exogenous addition of ApoD to HT-29 cells does not modify proliferation or apoptosis levels in control conditions, but it promotes apoptosis upon paraquat-induced OS.

Conclusion

Our results show ApoD as a gene responding to OS in the tumor microenvironment. Besides using ApoD as marker of initial stages of tumor progression, it can become a therapeutic tool promoting death of proliferating tumor cells suffering OS.

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Title: Expression and potential role of apolipoprotein D on the death–survival balance of human colorectal cancer cells under oxidative stress conditions
Authors: Raquel Bajo-Grañeras
Jesús Crespo-Sanjuan
Rosa M. García-Centeno
José Antonio Garrote-Adrados
Gabriel Gutierrez
Manuel García-Tejeiro
Beatriz Aguirre-Gervás
María D. Calvo-Nieves
Rosa Bustamante
Maria D. Ganfornina
Diego Sanchez
Publication date: 01-06-2013
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 6/2013
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-012-1616-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expression and potential role of apolipoprotein D on the death–survival balance of human colorectal cancer cells under oxidative stress conditions

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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