Global secretome analysis identifies novel mediators of bone metastasis.

TitleGlobal secretome analysis identifies novel mediators of bone metastasis.
Publication TypeJournal Articles
Year of Publication2012
AuthorsBlanco MAndres, LeRoy G, Khan Z, Alečković M, Zee BM, Garcia BA, Kang Y
JournalCell Res
Date Published2012 Sep
KeywordsAnimals, Biomarkers, Tumor, Bone Neoplasms, Cell Line, Tumor, Collagen Type VI, Computational Biology, HUMANS, Mass Spectrometry, Mice, Neoplasms, Plasminogen Activators, Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase, Proteome, proteomics, Salivary Cystatins

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 plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

Alternate JournalCell Res.
PubMed ID22688892
PubMed Central IDPMC3434351
Grant ListDP2OD007447 / OD / NIH HHS / United States
R01 CA134519 / CA / NCI NIH HHS / United States
R01 CA141062 / CA / NCI NIH HHS / United States
R01CA134519 / CA / NCI NIH HHS / United States
R01CA141062 / CA / NCI NIH HHS / United States