Leveraging ectopic Hsp90 expression to assay the presence of tumor cells and aggressive tumor phenotypes in breast specimens

Sci Rep. 2017 Dec 13;7(1):17487. doi: 10.1038/s41598-017-17832-x.

Abstract

Hsp90 has been studied extensively as a therapeutic target in breast cancer in pre-clinical and clinical trials, demonstrating a variety of roles in metastatic progression. The evidence to date suggests a compelling opportunity to leverage attributes of Hsp90 expression beyond therapeutics with potential applications in breast cancer diagnosis, prognosis, and recurrence risk assessment. In this study, we developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay Hsp90 expression on intact tissue specimens with comparable contrast to in vivo administration routes, and demonstrate the feasibility of our approach in breast cancer patients. In addition to Hsp90 inhibition being most effective in glycolytic tumors, we found ectopic Hsp90 expression to be highest in glycolytic tumors reinforcing its role as an indicator of aggressive disease. This work sets the stage for immediately using Hsp90 to improve outcomes for breast cancer patients without affecting traditional care pathways.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Biopsy, Large-Core Needle
  • Breast / diagnostic imaging
  • Breast / metabolism*
  • Breast / pathology
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Female
  • Fluorescent Dyes*
  • Glycolysis
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Mice, Nude
  • Neoplasm Transplantation
  • Optical Imaging
  • Oxidation-Reduction
  • Receptor, ErbB-2 / metabolism
  • Ultrasonography, Interventional
  • Ultrasonography, Mammary

Substances

  • Biomarkers, Tumor
  • Fluorescent Dyes
  • HSP90 Heat-Shock Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2