Aromatase inhibitor-induced bone loss increases the progression of estrogen receptor-negative breast cancer in bone and exacerbates muscle weakness in vivo

作者：Laura E. Wright, Ahmed Harhash, Wende Kozlow, David L. Waning, Jenna N. Regan, Yun She, Sutha K. John, Sreemala Murthy, Maryla Niewolna, Andrew R. Marks, Khalid S. Mohammad, Theresa A. Guise · 发表于：Oncotarget · 年份：2016 · DOI：10.18632/oncotarget.14139 · 被引用次数：37 · 研究领域：Estrogen and related hormone effects、Bone health and treatments、Endometrial and Cervical Cancer Treatments

// Laura E. Wright 1 , Ahmed A. Harhash 1 , Wende M. Kozlow 2 , David L. Waning 3 , Jenna N. Regan 1 , Yun She 1 , Sutha K. John 1 , Sreemala Murthy 1 , Maryla Niewolna 1 , Andrew R. Marks 4 , Khalid S. Mohammad 1 , Theresa A. Guise 1 1 Department of Medicine, Division of Endocrinology, Indiana University, Indianapolis, IN, USA 2 Department of Internal Medicine, Division of Endocrinology, University of Virginia, Charlottesville, VA, USA 3 Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA 4 Department of Physiology, Columbia University, New York, NY, USA Correspondence to: Laura E. Wright, email: laewrig@iu.edu Keywords: breast cancer, bone, metastasis, aromatase inhibitor, skeletal muscle Received: October 20, 2016      Accepted: November 23, 2016      Published: December 25, 2016 ABSTRACT Aromatase inhibitors (AIs) cause muscle weakness, bone loss, and joint pain in up to half of cancer patients. Preclinical studies have demonstrated that increased osteoclastic bone resorption can impair muscle contractility and prime the bone microenvironment to accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Female athymic nude mice underwent ovariectomy (OVX) or sham surgery and were treated with vehicle or AI (letrozole; Let). An OVX-...