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Cancer Res. 2017 Jun 15;77(12):3144-3150. doi: 10.1158/0008-5472.CAN-16-0708. Epub 2017 Apr 20.

Interaction between Tumor Cell Surface Receptor RAGE and Proteinase 3 Mediates Prostate Cancer Metastasis to Bone.

Author information

1
The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas. Mikhail.G.Kolonin@uth.tmc.edu rpasqual@salud.unm.edu warap@salud.unm.edu.
2
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
3
University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.
4
Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico.
5
Department of Neurology, Harvard Medical School, Boston, Massachusetts.
6
Department of Oncology, University of Turin, Candiolo, Italy.
7
Candiolo Cancer Center-FPO, IRCCS, Candiolo, Italy.
8
University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico. Mikhail.G.Kolonin@uth.tmc.edu rpasqual@salud.unm.edu warap@salud.unm.edu.
9
Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico.

Abstract

Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in vitro, inducing tumor cell motility through a nonproteolytic signal transduction cascade involving activation and phosphorylation of ERK1/2 and JNK1. In preclinical models of experimental metastasis, ectopic expression of RAGE on human prostate cancer cells was sufficient to promote bone marrow homing within a short timeframe. Our findings demonstrate how RAGE-PR3 interactions between human prostate cancer cells and the bone marrow microenvironment mediate bone metastasis during prostate cancer progression, with potential implications for prognosis and therapeutic intervention. Cancer Res; 77(12); 3144-50. ©2017 AACR.

PMID:
28428279
PMCID:
PMC5858698
DOI:
10.1158/0008-5472.CAN-16-0708
[Indexed for MEDLINE]
Free PMC Article

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