RRC ID |
67419
|
著者 |
Asanuma D, Sakabe M, Kamiya M, Yamamoto K, Hiratake J, Ogawa M, Kosaka N, Choyke PL, Nagano T, Kobayashi H, Urano Y.
|
タイトル |
Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo.
|
ジャーナル |
Nat Commun
|
Abstract |
Fluorescence-guided diagnostics is one of the most promising approaches for facile detection of cancer in situ. Here we focus on β-galactosidase, which is overexpressed in primary ovarian cancers, as a molecular target for visualizing peritoneal metastases from ovarian cancers. As existing fluorescence probes are unsuitable, we have designed membrane-permeable HMRef-βGal, in which the optimized intramolecular spirocyclic function affords >1,400-fold fluorescence enhancement on activation. We confirm that HMRef-βGal sensitively detects intracellular β-galactosidase activity in several ovarian cancer lines. In vivo, this probe visualizes metastases as small as <1 mm in diameter in seven mouse models of disseminated human peritoneal ovarian cancer (SHIN3, SKOV3, OVK18, OVCAR3, OVCAR4, OVCAR5 and OVCAR8). Because of its high brightness, real-time detection of metastases with the naked eye is possible. Endoscopic fluorescence detection of metastases is also demonstrated. The results clearly indicate preclinical potential value of the probe for fluorescence-guided diagnosis of peritoneal metastases from ovarian cancers.
|
巻・号 |
6
|
ページ |
6463
|
公開日 |
2015-3-13
|
DOI |
10.1038/ncomms7463
|
PII |
ncomms7463
|
PMID |
25765713
|
PMC |
PMC4382686
|
MeSH |
Animals
Disease Models, Animal
Endoscopy
Female
Fluorescent Dyes / chemistry*
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Inbred BALB C
Microscopy, Fluorescence
Neoplasm Metastasis
Ovarian Neoplasms / diagnosis*
Ovarian Neoplasms / pathology
Peritoneal Neoplasms / diagnosis*
Peritoneal Neoplasms / secondary
beta-Galactosidase / metabolism*
|
IF |
12.121
|
リソース情報 |
ヒト・動物細胞 |
NIH:OVCAR-3(RCB2135)
OVK18(RCB1903) |