title: Peroxiredoxin 4: a novel secreted mediator of cancer induced osteoclastogenesis.
abstract: Bone is a common site of metastasis from breast and prostate carcinoma, where activation of bone resorbing osteoclasts is important for cancer progression. A large body of evidence indicates that soluble factors produced by the cancer cells act to promote osteoclast formation. Using mass spectrometry, we identified peroxiredoxin (PRDX) as a secreted mediator of cancer-induced osteoclastogenesis. Both breast (MCF7 and MDA-MB-231) and prostate (PC3 and LNCaP) carcinoma cells secreted PRDX4. PRDX4 knockdown using shRNA (shPRDX4) diminished PRDX4 secretion from MDA-MB-231 and PC3 cells and significantly decreased the ability of cancer-derived factors to induce osteoclast formation from late precursors in vitro. Tibial injection of shPRDX4 PC3 cells led to the development of significantly smaller osteolytic lesions characterized by significantly reduced osteoclast numbers compared to control PC3 cells. A meta-analysis demonstrated an increase in PRDX4 mRNA expression in carcinoma and metastatic breast and prostate tissues. Moreover, high expression of PRDX4 in the primary breast tumor was consistently associated with metastasis at 5 years. These data identify a novel function of secreted PRDX4 in mediating osteoclast activation by cancer cells.
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montréal, Quebec, Canada; Shriners Hospital for Children-Canada, Montréal, Quebec H3G IA6, Canada.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Rafiei
authors.affiliation: Shriners Hospital for Children-Canada, Montréal, Quebec H3G IA6, Canada; Faculty of Dentistry, McGill University, Montréal, Quebec, Canada.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Tiedemann
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Quebec, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Tabariès
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Quebec, Canada; Department of Biochemistry, McGill University, Montréal, Quebec, Canada; Department of Medicine, McGill University, Montréal, Quebec, Canada.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siegel
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montréal, Quebec, Canada; Shriners Hospital for Children-Canada, Montréal, Quebec H3G IA6, Canada; Faculty of Dentistry, McGill University, Montréal, Quebec, Canada. Electronic address: svetlana.komarova@mcgill.ca.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Komarova
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis; D054464:Peroxiredoxins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C515980:PRDX4 protein, human; D054464:Peroxiredoxins
keywords: Bone; Breast cancer; Metastasis; Osteoclast; PRDX4; Prostate cancer