Oncotarget

Research Papers:

ZIP4 silencing improves bone loss in pancreatic cancer

Qiang Zhang, Xiaotian Sun, Jingxuan Yang, Hao Ding, Drake LeBrun, Kai Ding, Courtney W. Houchen, Russell G. Postier, Catherine G. Ambrose, Zhaoshen Li, Xiaohong Bi _ and Min Li

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Oncotarget. 2015; 6:26041-26051. https://doi.org/10.18632/oncotarget.4667

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Abstract

Qiang Zhang1,2,*, Xiaotian Sun2,3,4,5,*, Jingxuan Yang2,4,5, Hao Ding6, Drake LeBrun2, Kai Ding7, Courtney W. Houchen4, Russell G. Postier5, Catherine G. Ambrose8, Zhaoshen Li3, Xiaohong Bi6, Min Li2,4,5

1Department of Orthopedics, General Hospital of the Jinan Military Command, Jinan, Shandong 250031, China

2The Vivian L. Smith Department of Neurosurgery, the University of Texas Medical School at Houston, Houston, TX 77030, USA

3Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China

4Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

5Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

6Department of Nanomedicine and Biomedical Engineering, the University of Texas Medical School at Houston, Houston, TX 77030, USA

7Department of Biostatistics and Epidemiology, College of Public Health, the University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

8Department of Orthopedic Surgery, the University of Texas Medical School at Houston, Houston, TX 77030, USA

*These authors have contributed equally to this work

Correspondence to:

Xiaohong Bi, e-mail: [email protected]

Zhaoshen Li, e-mail: [email protected]

Min Li, e-mail: [email protected]

Keywords: ZIP4, bone, cachexia, pancreatic cancer, RANK/RANKL signaling

Received: May 10, 2015     Accepted: July 06, 2015     Published: July 20, 2015

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.


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