title: Differential proteomic analysis of a human breast tumor and its matched bone metastasis identifies cell membrane and extracellular proteins associated with bone metastasis.
abstract: The classical fate of metastasizing breast cancer cells is to seed and form secondary colonies in bones. The molecules closely associated with these processes are predominantly present at the cell surface and in the extracellular space, establishing the first contacts with the target tissue. In this study, we had the rare opportunity to analyze a bone metastatic lesion and its corresponding breast primary tumor obtained simultaneously from the same patient. Using mass spectrometry, we undertook a proteomic study on cell surface and extracellular protein-enriched material. We provide a repertoire of significantly modulated proteins, some with yet unknown roles in the bone metastatic process as well as proteins notably involved in cancer cell invasiveness and in bone metabolism. The comparison of these clinical data with those previously obtained using a human osteotropic breast cancer cell line highlighted an overlapping group of proteins. Certain differentially expressed proteins are validated in the present study using immunohistochemistry on a retrospective collection of breast tumors and matched bone metastases. Our exclusive set of selected proteins supports the setup of further investigations on both clinical samples and experimental bone metastasis models that will help to reveal the finely coordinated expression of proteins that favor the development of metastases in the bone microenvironment.
authors.affiliation: Metastasis Research Laboratory, Department of Pathology, University of Liège, Bat. B23, CHU Sart Tilman Liège, B-4000 Liège, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dumont
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
authors.forename: Olivier
authors.initials: O
authors.lastname: Peulen
authors.forename: Noëlla
authors.initials: N
authors.lastname: Blétard
authors.forename: Philippe
authors.initials: P
authors.lastname: Clézardin
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Edwin A
authors.initials: EA
authors.lastname: De Pauw
authors.forename: Andrei
authors.initials: A
authors.lastname: Turtoi
authors.forename: Akeila
authors.initials: A
authors.lastname: Bellahcène
mesh_terms: D001859:Bone Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000556:secondary*; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
chemical_list: D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins