Quantitative mitochondrial redox imaging of breast cancer metastatic potential

Quantitative mitochondrial redox imaging of breast cancer metastatic potential
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DOI:
10.1117/1.3431714
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发表时间:
2010-05-01
影响因子:
3.5
通讯作者:
Li, Lin Z.
Li, Lin Z.
中科院分区:
医学3区
文献类型:
--
作者:
Xu, He N.;Nioka, Shoko;Li, Lin Z.

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预测肿瘤转移潜能在癌症研究和临床实践中仍然是一个挑战。我们的目标是通过成像肿瘤组织体内线粒体的氧化还原状态来识别区分不同转移潜能的人类乳腺肿瘤的新的生物标志物。用低温氧化还原扫描仪对转移较多(侵袭性)的MDA-MB-231和转移较少(惰性)的MCF-7人乳腺癌小鼠移植瘤进行成像,以获得还原烟酰胺腺嘌呤二核苷酸(NADH)和氧化黄素蛋白(FP)的多层荧光图像。使用参考标准测量组织中NADH和FP的标称浓度,并用于计算FP氧化还原比FP/(NADH+FP)。我们观察到了显著的核心-边缘差异,在所有侵袭性肿瘤中,核心比边缘氧化得更多,但在惰性肿瘤中则不是。这些结果与我们之前对人黑色素瘤小鼠移植瘤的观察结果一致,表明线粒体氧化还原成像可能为区分侵袭性和惰性乳腺肿瘤移植提供了敏感的标记物。线粒体氧化还原成像可以利用低温活检标本在临床上实现,并有助于药物开发和乳腺癌的临床诊断。(C)2010年光学仪器工程师学会。[DOI:10.1117/1.3431714]
Predicting tumor metastatic potential remains a challenge in cancer research and clinical practice. Our goal was to identify novel biomarkers for differentiating human breast tumors with different metastatic potentials by imaging the in vivo mitochondrial redox states of tumor tissues. The more metastatic (aggressive) MDA-MB-231 and less metastatic (indolent) MCF-7 human breast cancer mouse xenografts were imaged with the low-temperature redox scanner to obtain multi-slice fluorescence images of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp). The nominal concentrations of NADH and Fp in tissue were measured using reference standards and used to calculate the Fp redox ratio, Fp/(NADH+Fp). We observed significant core-rim differences, with the core being more oxidized than the rim in all aggressive tumors but not in the indolent tumors. These results are consistent with our previous observations on human melanoma mouse xenografts, indicating that mitochondrial redox imaging potentially provides sensitive markers for distinguishing aggressive from indolent breast tumor xenografts. Mitochondrial redox imaging can be clinically implemented utilizing cryogenic biopsy specimens and is useful for drug development and for clinical diagnosis of breast cancer. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3431714]