Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikisReportar como inadecuado




Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Molecular Cancer

, 9:206

First Online: 03 August 2010Received: 27 May 2010Accepted: 03 August 2010

Abstract

BackgroundThe metastatic spread of solid tumors is directly or indirectly responsible for most cancer-related deaths. Tumor metastasis is very complex and this process requires a tumor cell to acquire enhanced motility, invasiveness and anoikis resistance to successfully establish a tumor at a distal site. Metastatic potential of tumor cells is directly correlated with the expression levels of several angiogenic cytokines. Copper is a mandatory cofactor for the function of many of these angiogenic mediators as well as other proteins that play an important role in tumor cell motility and invasiveness. We have previously shown that tetrathiomolybdate TM is a potent chelator of copper and it mediates its anti-tumor effects by suppressing tumor angiogenesis. However, very little is known about the effect of TM on tumor cell function and tumor metastasis. In this study, we explored the mechanisms underlying TM-mediated inhibition of tumor metastasis.

ResultsWe used two in vivo models to examine the effects of TM on tumor metastasis. Animals treated with TM showed a significant decrease in lung metastasis in both in vivo models as compared to the control group. In addition, tumor cells from the lungs of TM treated animals developed significantly smaller colonies and these colonies had significantly fewer tumor cells. TM treatment significantly decreased tumor cell motility and invasiveness by inhibiting lysyl oxidase LOX activity, FAK activation and MMP2 levels. Furthermore, TM treatment significantly enhanced tumor cell anoikis by activating p38 MAPK cell death pathway and by downregulating XIAP survival protein expression.

ConclusionsTaken together, these results suggest that TM is a potent suppressor of head and neck tumor metastasis by modulating key regulators of tumor cell motility, invasiveness and anoikis resistance.

AbbreviationsHNSCChead and neck squamous cell carcinoma

OSCC-3oral squamous cell carcinoma-3

ECendothelial cell

TMtetrathiomolybdate

FAKfocal adhesion kinase

LOXlysyl oxidase

XIAPX-linked Inhibitor of Apoptosis Protein

VEGFvascular endothelial cell growth factor

SCIDSevere combined immunodeficiency disease

MMPMatrix metalloproteinases.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-9-206 contains supplementary material, which is available to authorized users.

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Autor: Pawan Kumar - Arti Yadav - Samip N Patel - Mozaffarul Islam - Quintin Pan - Sofia D Merajver - Theodoros N Teknos

Fuente: https://link.springer.com/







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