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Osteopontin expression correlates with nuclear factor-κ B activation and apoptosis downregulation in clear cell renal cell carcinoma

Osteopontin (OPN) is a phosphoglycoprotein implicated in tumourigenesis and tumour cell metastasis. Apoptosis inhibition is one of the mechanisms that contribute to development and progression of cancer, and might be initiated by OPN interaction with tumour cell. The aim of this study was to analyse the relation between OPN and nuclear factor-kappa B (NF-κB) expression in clear cell renal cell carcinoma (CCRCC), as well as their relation to apoptotic activity of tumour cells. Expression of OPN protein and p65 NF-κB subunit was analyzed immunohistochemicaly in 87 CCRCC samples, and compared mutually and to apoptotic index. Expression of OPN mRNA was analyzed using quantitative real-time PCR and compared to OPN and NF-κB protein expression in 22 CCRCC samples. Statistical analysis showed the association of p65 NF-κB with OPN mRNA (p=0.015) and protein (p<0.001). Also, we found the inverse relationship of OPN and NF-κB protein expression and apoptotic activity of tumour cells (p=0.006 and p=0.022, respectively). Our results indicate that p65 NF-κB signaling pathway may be involved in OPN-mediated CCRCC progression, partly by protecting tumour cells from apoptosis. Therefore, both molecules can constitute potential targets for therapeutic intervention in CCRCC.

apoptosis; renal cell carcinoma; nuclear factor kappa B; osteopontin; tissue array analysis

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