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Proteomic Identification of Haptoglobin alpha 2 as a Glioblastoma Serum Biomarker: Implications in Cancer Cell Migration and Tumor Growth

Kumar, Durairaj Mohan and Thota, Balaram and Shinde, Sridevi Vijay and Prasanna, KV and Hegde, AS and Arivazhagan, A and Chandramouli, BA and Santosh, Vani and Somasundaram, Kumaravel (2010) Proteomic Identification of Haptoglobin alpha 2 as a Glioblastoma Serum Biomarker: Implications in Cancer Cell Migration and Tumor Growth. In: Journal of Proteome Research, 9 (11). pp. 5557-5567.

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Official URL: http://pubs.acs.org/doi/abs/10.1021/pr1001737

Abstract

Glioblastoma (GBM; grade IV astrocytoma) is the most malignant and common primary brain tumor in adults. Using combination of 2-DE and MALDI-TOF MS, we analyzed 14 GBM and 6 normal control sera and identified haptoglobin alpha 2 chain as an up-regulated serum protein in GBM patients. GBM-specific up-regulation was confirmed by ELISA based quantitation of haptoglobin (Hp) in the serum of 99 GBM patients as against lower grades (49 grade III/AA; 26 grade II/DA) and 26 normal individuals (p = 0.0001). Further validation using RT-qPCR on an independent set (n = 78) of tumor and normal brain (n = 4) samples and immunohistochemcial staining on a subset (n = 42) of above samples showed increasing levels of transcript and protein with tumor grade and were highest in GBM (p = < 0.0001 and < 0.0001, respectively). Overexpression of Hp either by stable integration of Hp cDNA or exogenous addition of purified Hp to immortalized astrocytes resulted in increased cell migration. RNAi-mediated silencing of Hp in glioma cells decreased cell migration. Further, we demonstrate that both human glioma and mouse melanoma cells overexpressing Hp showed increased tumor growth. Thus, we have identified haptoglobin as a GBM-specific serum marker with a role on glioma tumor growth and migration.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to American Chemical Society.
Keywords: astrocytoma; glioma; glioblastoma; haptoglobin; migration; proteomics; 2-DE; MALDI-TOF MS; serum biomarker
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 23 Dec 2010 09:25
Last Modified: 23 Dec 2010 09:25
URI: http://eprints.iisc.ernet.in/id/eprint/34310

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