TY - JOUR
T1 - MicroPET/CT imaging of AXL downregulation by HSP90 inhibition in triple-negative breast cancer
AU - Wang, Wanqin
AU - Zhao, Jun
AU - Wen, Xiaoxia
AU - Chun-Jen Lin, Curtis
AU - Li, Junjie
AU - Huang, Qian
AU - Yu, Yongqiang
AU - Lin, Shiaw Yih
AU - Li, Chun
N1 - Publisher Copyright:
© 2017 WanqinWang et al.
PY - 2017/5/14
Y1 - 2017/5/14
N2 - 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 with64Cu-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-AAGtreatment caused significant decline in AXL expression in orthotopic TNBCMDA-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 that64Cu-anti-hAXL can be useful for monitoring anti-AXL therapies and for assessing inhibition of HSP90 molecular chaperone using AXL as a molecular surrogate.
AB - 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 with64Cu-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-AAGtreatment caused significant decline in AXL expression in orthotopic TNBCMDA-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 that64Cu-anti-hAXL can be useful for monitoring anti-AXL therapies and for assessing inhibition of HSP90 molecular chaperone using AXL as a molecular surrogate.
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U2 - 10.1155/2017/1686525
DO - 10.1155/2017/1686525
M3 - Article
C2 - 29097911
AN - SCOPUS:85020173559
SN - 1555-4309
VL - 2017
JO - Contrast Media and Molecular Imaging
JF - Contrast Media and Molecular Imaging
M1 - 1686525
ER -