論文

2017年10月9日

In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior.

Clinical cancer research : an official journal of the American Association for Cancer Research
  • Osada T
  • ,
  • Kaneko K
  • ,
  • Gwin WR
  • ,
  • Morse MA
  • ,
  • Hobeika A
  • ,
  • Pogue BW
  • ,
  • Hartman ZC
  • ,
  • Hughes PF
  • ,
  • Haystead T
  • ,
  • Herbert Kim Lyerly

記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1158/1078-0432.ccr-17-1453, 10.1158/1078-0432.CCR-17-1453

Purpose: Hsp90, a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers. We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive breast cancers.Experimental Design: We exploited the uptake of an Hsp90 inhibitor by malignant cells to create an imaging probe (HS131) of Hsp90 activity by linking it to a near-infrared (nIR) dye. HS131 uptake into cells correlated with cell membrane expression of Hsp90 and was used to image molecular subtypes of murine and human breast cancers in vitro and in murine models.Results: HS131 imaging was both sensitive and specific in detecting the murine 4T1 breast cancer cell line, as well as subclones with differing metastatic potential. Highly metastatic subclones (4T07) had high HS131 uptake, but subclones with lower metastatic potential (67NR, 168FARN) had low HS131 uptake. We generated isogenic cell lines to demonstrate that overexpression of a variety of specific oncogenes resulted in high HS131 uptake and retention. Finally, we demonstrated that HS131 could be used to detect spontaneous tumors in MMTV-neu mice, as well as primary and metastatic human breast cancer xenografts. HS131 could image invasive lobular breast cancer, a histologic subtype of breast cancer which is often undetectable by mammography.Conclusions: An HSP90-targeting nIR probe is sensitive and specific in imaging all molecular subtypes of murine and human breast cancer, with higher uptake in aggressive and highly metastatic clones. Clinical studies with Hsp90-targeting nIR probes will be initiated shortly. Clin Cancer Res; 23(24); 7531-42. ©2017 AACR.

リンク情報
DOI
https://doi.org/10.1158/1078-0432.ccr-17-1453
DOI
https://doi.org/10.1158/1078-0432.CCR-17-1453
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28993342
ID情報
  • DOI : 10.1158/1078-0432.ccr-17-1453
  • DOI : 10.1158/1078-0432.CCR-17-1453
  • ORCIDのPut Code : 136783539
  • PubMed ID : 28993342

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