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Oncotarget. 2015 Sep 22;6(28):26041-51. doi: 10.18632/oncotarget.4667.

ZIP4 silencing improves bone loss in pancreatic cancer.

Author information

1
Department of Orthopedics, General Hospital of The Jinan Military Command, Jinan, Shandong 250031, China.
2
The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
3
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
4
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
5
Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
6
Department of Nanomedicine and Biomedical Engineering, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
7
Department of Biostatistics and Epidemiology, College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
8
Department of Orthopedic Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA.

Abstract

Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders.

KEYWORDS:

RANK/RANKL signaling; ZIP4; bone; cachexia; pancreatic cancer

PMID:
26305676
PMCID:
PMC4694884
DOI:
10.18632/oncotarget.4667
[Indexed for MEDLINE]
Free PMC Article

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