MicroPET/CT Imaging of AXL Downregulation by HSP90 Inhibition in Triple-Negative Breast Cancer
Abstract
AXL receptor tyrosine kinase is overexpressed in a number of solid tumor types including triple-negative breast cancer (TNBC). AXL is considered an important regulator of epithelial-to-mesenchymal transition (EMT) and a potential therapeutic target for TNBC. In this work, we used microPET/CT with 64Cu-labeled anti-human AXL antibody (64Cu-anti-hAXL) to noninvasively interrogate the degradation of AXL in vivo in response to 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent inhibitor of HSP90. 17-AAG treatment caused significant decline in AXL expression in orthotopic TNBC MDA-MB-231 tumors, inhibited EMT, and delayed tumor growth in vivo, resulting in significant reduction in tumor uptake of 64Cu-anti-hAXL as clearly visualized by microPET/CT. Our data indicate that 64Cu-anti-hAXL can be useful for monitoring anti-AXL therapies and for assessing inhibition of HSP90 molecular chaperone using AXL as a molecular surrogate.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2017
- Source ID
- 10.1155/2017/1686525
Entities
People
- Chun Li
- Curtis Chun-jen Lin
- Jun Zhao
- Junjie Li
- Qian Huang
- Shiaw-Yih Lin
- Wanqin Wang
- Xiaoxia Wen
- Yongqiang Yu
Organizations
- Anhui Medical University
- United States Department of Defense
- University of Texas at Austin