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Global secretome analysis identifies novel mediators of bone metastasis

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Global secretome analysis identifies novel

mediators of bone metastasis

Mario Andres Blanco;Gary LeRoy;Zia Khan;Ma(s)a Ale(c)kovi(c);Barry M Zee;Benjamin A Garcia;Yibin Kang

【期刊名称】《细胞研究(英文版)》 【年(卷),期】2012(022)009

【摘要】Bone is the one of the most common sites of distant metastasis of solid tumors.Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma.To comprehensively profile secreted proteins associated with bone metastasis,we

used

quantitative

and

non-quantitative

mass

spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types.By comparing the secretomes of parental cells and their bone metastatic derivatives,we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines.We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis.Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1,CST2,and CST4; (2) the

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