Glunde Kristine, Foss Catherine A, Takagi Tomoyo, Wildes Flonne, Bhujwalla Zaver M
JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Bioconjug Chem. 2005 Jul-Aug;16(4):843-51. doi: 10.1021/bc050046n.
Lysosomes contain multiple proteases, which play a crucial role in breast cancer invasion and metastasis. Noninvasive labeling of lysosomes in breast cancer cells and solid breast tumor models is therefore useful to study lysosomal trafficking and its role in invasion. We have synthesized a novel compound, 6'-O-lissamine-rhodamine B-glucosamine, to fluorescently label lysosomes, and evaluated the compound in human breast cancer cells in cell culture or in orthotopic human breast cancer models. We demonstrated that this novel compound biosynthetically labeled lysosomal proteins following addition to cell culture medium or following intravenous injection into mouse models of breast cancer. Fluorescence from 6'-O-lissamine-rhodamine B-glucosamine colocalized with several well-established lysosomal markers, such as lysosome-associated proteins 1 and 2 (LAMP-1 and -2) and CD63. We also demonstrated the feasibility of performing in vivo fluorescence imaging of 6'-O-lissamine-rhodamine B-glucosamine to image lysosomes in human breast cancer models.
溶酶体含有多种蛋白酶，它们在乳腺癌的侵袭和转移中起着关键作用。因此，对乳腺癌细胞和实体乳腺肿瘤模型中的溶酶体进行非侵入性标记，有助于研究溶酶体运输及其在侵袭中的作用。我们合成了一种新型化合物6'-O-丽丝胺罗丹明B-葡糖胺，用于对溶酶体进行荧光标记，并在细胞培养中的人乳腺癌细胞或原位人乳腺癌模型中对该化合物进行了评估。我们证明，在将该新型化合物添加到细胞培养基中或静脉注射到乳腺癌小鼠模型后，它能通过生物合成标记溶酶体蛋白。6'-O-丽丝胺罗丹明B-葡糖胺发出的荧光与几种公认的溶酶体标记物共定位，如溶酶体相关蛋白1和2（LAMP-1和LAMP-2）以及CD63。我们还证明了对6'-O-丽丝胺罗丹明B-葡糖胺进行体内荧光成像以对人乳腺癌模型中的溶酶体进行成像的可行性。
