Fujita Kyohhei, Kamiya Mako, Yoshioka Takafusa, Ogasawara Akira, Hino Rumi, Kojima Ryosuke, Ueo Hiroaki, Urano Yasuteru
Graduate School of Medicine and Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
ACS Cent Sci. 2020 Dec 23;6(12):2217-2227. doi: 10.1021/acscentsci.0c01189. Epub 2020 Oct 29.
Accurate detection of breast tumors and discrimination of tumor from normal tissues during breast-conserving surgery are essential to reduce the risk of misdiagnosis or recurrence. However, existing probes show substantial background signals in normal breast tissues. In this study, we focus on glycosidase activities in breast tumors. We synthesized a series of 12 fluorescent probes and performed imaging-based evaluation on surgically resected human breast specimens. Among them, the α-mannosidase-reactive fluorescent probe HMRef-αMan detected breast cancer with 90% sensitivity and 100% specificity. We identified α-mannosidase 2C1 as the target enzyme and confirmed its overexpression in various breast tumors. We found that fibroadenoma, the most common benign breast lesion in young woman, tends to have higher α-mannosidase 2C1 activity than malignant cancer. Combined application of green-emitting HMRef-αMan and a red-emitting γ-glutamyltranspeptidase probe enabled efficient dual-color, dual-target optical discrimination of malignant and benign tumors.
在保乳手术期间准确检测乳腺肿瘤并区分肿瘤与正常组织对于降低误诊或复发风险至关重要。然而，现有的探针在正常乳腺组织中显示出大量背景信号。在本研究中，我们聚焦于乳腺肿瘤中的糖苷酶活性。我们合成了一系列12种荧光探针，并对手术切除的人类乳腺标本进行了基于成像的评估。其中，α-甘露糖苷酶反应性荧光探针HMRef-αMan检测乳腺癌的灵敏度为90%，特异性为100%。我们确定α-甘露糖苷酶2C1为靶酶，并证实其在各种乳腺肿瘤中过表达。我们发现，纤维腺瘤是年轻女性中最常见的良性乳腺病变，其α-甘露糖苷酶2C1活性往往高于恶性肿瘤。绿色发射的HMRef-αMan与红色发射的γ-谷氨酰转肽酶探针的联合应用能够实现对恶性和良性肿瘤的高效双色、双靶点光学鉴别。
