Heptamethine carbocyanine dye-mediated near-infrared imaging of canine and human cancers through the HIF-1α/OATPs signaling axis.
Heptamethine carbocyanine dye-mediated near-infrared imaging of canine and human cancers through the HIF-1α/OATPs signaling axis.
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DOI：
10.18632/oncotarget.2464
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发表时间：
2014-10-30
期刊：
影响因子：
--
通讯作者：
Chung LW
中科院分区：
文献类型：
--
作者：
Shi C;Wu JB;Chu GC;Li Q;Wang R;Zhang C;Zhang Y;Kim HL;Wang J;Zhau HE;Pan D;Chung LW
近红外（NIR）荧光成像剂是用于非侵入性癌症成像的有前途的工具。本研究探讨了犬癌细胞和组织以及人前列腺癌（PCa）标本对NIR七甲川羰花青MHI-148染料的特异性摄取和保留以及染料摄取机制。通过NIR荧光显微镜和全身NIR光学成像，在犬癌细胞和组织以及异种移植到小鼠中的新鲜收获的人PCa组织中特异性检测到MHI-148的蓄积。通过PET成像进一步证实了犬自发性肿瘤中的特异性染料摄取。多重量子点标记和qPCR检测结果显示，肿瘤组织中缺氧诱导因子-1 α（HIF-1α）和有机阴离子转运多肽（OATP）蛋白和mRNA的表达均高于正常组织。用HIF-1α稳定剂处理癌细胞激活HIF-1α下游靶基因，诱导OATP超家族基因表达，并增强细胞对NIR染料的摄取和保留。此外，通过siRNA沉默HIF-1α显著降低了癌细胞中OATP mRNA的表达并阻断了NIR染料摄取。总之，这些结果证明了犬和人类癌细胞和组织通过HIF-1α/OATPs信号传导轴优先摄取NIR染料，这为这些染料在癌症检测和治疗中的未来应用提供了见解。
Near-infrared (NIR) fluorescence imaging agents are promising tools for noninvasive cancer imaging. This study explored the specific uptake and retention of a NIR heptamethine carbocyanine MHI-148 dye by canine cancer cells and tissues and human prostate cancer (PCa) specimens and also the dye uptake mechanisms. The accumulation of MHI-148 was detected specifically in canine cancer cells and tissues and freshly harvested human PCa tissues xenografted in mice by NIR fluorescence microscopy and whole-body NIR optical imaging. Specific dye uptake in canine spontaneous tumors was further confirmed by PET imaging. Higher hypoxia-inducible factor-1α (HIF-1α) and organic anion-transporting polypeptide (OATP) protein and mRNA expression was demonstrated by multiplex quantum dots labeling and qPCR in tumors over that of normal tissues. Treating cancer cells with HIF-1α stabilizers activated HIF-1α downstream target genes, induced OATP superfamily gene expression and enhanced cellular uptake and retention of NIR dyes. Moreover, silencing HIF-1α by siRNA significantly decreased OATP mRNA expression and blocked NIR dye uptake in cancer cells. Together, these results demonstrated the preferential uptake of NIR dyes by canine and human cancer cells and tissues via the HIF-1α/OATPs signaling axis, which provides insights into future application of these dyes for cancer detection and treatment.
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影响因子：
2.8
作者：
Thudi, Nanda K.;Shu, Sherry T.;Martin, Chelsea K.;Lanigan, Lisa G.;Nadella, Murali V. P.;Van Bokhoven, Adrie;Werbeck, Jillian L.;Simmons, Jessica K.;Murahari, Sridhar;Kisseberth, William C.;Breen, Matthew;Williams, Christina;Chen, Ching-Shih;McCauley, Laurie K.;Keller, Evan T.;Rosol, Thomas J.
通讯作者：
Rosol, Thomas J.
影响因子：
3.1
作者：
Marshall, Milton V.;Draney, Daniel;Sevick-Muraca, Eva M.;Olive, D. Michael
通讯作者：
Olive, D. Michael
影响因子：
4
作者：
Tamai, Ikumi;Nakanishi, Takeo
通讯作者：
Nakanishi, Takeo
影响因子：
3.1
作者：
Tsujino, Yoshio;Mizumoto, Kazuo;Morita, Eishin
通讯作者：
Morita, Eishin
DOI：
10.1146/annurev-pharmtox-010510-100556
发表时间：
2012
影响因子：
12.5
作者：
Obaidat A;Roth M;Hagenbuch B
通讯作者：
Hagenbuch B