Peroxiredoxin 4: a novel secreted mediator of cancer induced osteoclastogenesis

Cancer Letters
Shahrzad RafieiSvetlana V Komarova

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 c...Continue Reading

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Citations

Oct 13, 2015·Free Radical Biology & Medicine·Lucie ValekIrmgard Tegeder
Oct 27, 2016·International Journal of Molecular Sciences·Carrie S ShemankoAmanda Forsyth
Jul 18, 2019·Technology in Cancer Research & Treatment·Wenqiao JiaYufeng Cheng
Jun 21, 2019·Biochemistry. Biokhimii︠a︡·M G Sharapov, V I Novoselov
May 11, 2019·Clinical & Experimental Metastasis·Demond Williams, Barbara Fingleton
May 10, 2020·BioMed Research International·Rui XuQinglin Zhang
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Kerstin TiedemannSvetlana V Komarova
May 17, 2019·The Journal of Pathology·Fernando SalvadorRoger R Gomis
Sep 21, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ruihui XieTianxin Lin
Jan 19, 2021·Oxidative Medicine and Cellular Longevity·Jianbo ZhengSohsuke Yamada
Feb 16, 2021·Physiological Reports·Gulzhakhan SadvakassovaSvetlana V Komarova
Apr 20, 2021·Frontiers in Oncology·Domenica GiannandreaRaffaella Chiaramonte

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