Research ArticleCancer

The Secreted Protein ANGPTL2 Promotes Metastasis of Osteosarcoma Cells Through Integrin α5β1, p38 MAPK, and Matrix Metalloproteinases

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Science Signaling  21 Jan 2014:
Vol. 7, Issue 309, pp. ra7
DOI: 10.1126/scisignal.2004612

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Microenvironment Drives Osteosarcoma Metastasis

The selective pressures of the tumor microenvironment alter the behavior of cancer cells. Odagiri et al. found that the expression of ANGPTL2, encoding the secreted angiopoietin-like protein 2, increased in osteosarcoma cells grown in xenografts in mice or cultured in conditions that mimic the tumor microenvironment. Silencing ANGPTL2 or overexpressing a proteolytically cleaved form decreased matrix metalloproteinase-9 (MMP-9) activity, delayed the onset of metastasis from xenografts, and prolonged survival in mice. The abundance of ANGPTL2 correlated with that of MMP-9 in patient samples, and both inversely correlated with metastasis-free survival in patients. The findings highlight the influence of the tumor microenvironment and implicate ANGPTL2 as a target to hinder metastasis in osteosarcoma.

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