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ACS Chem Biol. 2017 Apr 21;12(4):1047-1055. doi: 10.1021/acschembio.7b00006. Epub 2017 Feb 23.

A Fluorescent Hsp90 Probe Demonstrates the Unique Association between Extracellular Hsp90 and Malignancy in Vivo.

Author information

1
Department of Cell Biology, Duke University , Durham, North Carolina 27710, United States.
2
Department of Pharmacology and Cancer Biology, Duke University , Durham, North Carolina 27710, United States.
3
Department of Medicine, Duke University , Durham, North Carolina 27710, United States.
4
Department of Surgery, Duke University , Durham, North Carolina 27710, United States.
5
BioInVision, Inc. , Mayfield Village, Ohio 44143, United States.
6
Lineberger Comprehensive Cancer Center, University of North Carolina , Chapel Hill, North Carolina 27599, United States.

Abstract

Extracellular expression of heat shock protein 90 (eHsp90) by tumor cells is correlated with malignancy. Development of small molecule probes that can detect eHsp90 in vivo may therefore have utility in the early detection of malignancy. We synthesized a cell impermeable far-red fluorophore-tagged Hsp90 inhibitor to target eHsp90 in vivo. High resolution confocal and lattice light sheet microscopy show that probe-bound eHsp90 accumulates in punctate structures on the plasma membrane of breast tumor cells and is actively internalized. The extent of internalization correlates with tumor cell aggressiveness, and this process can be induced in benign cells by overexpressing p110HER2. Whole body cryoslicing, imaging, and histology of flank and spontaneous tumor-bearing mice strongly suggests that eHsp90 expression and internalization is a phenomenon unique to tumor cells in vivo and may provide an "Achilles heel" for the early diagnosis of metastatic disease and targeted drug delivery.

PMID:
28103010
DOI:
10.1021/acschembio.7b00006
[Indexed for MEDLINE]

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