In vivo optical imaging of MMP2 immuno protein antibody: tumor uptake is associated with MMP2 activity.
In vivo optical imaging of MMP2 immuno protein antibody: tumor uptake is associated with MMP2 activity.
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DOI：
10.1038/srep22198
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发表时间：
2016-02-29
影响因子：
4.6
通讯作者：
Lambin P
中科院分区：
文献类型：
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作者：
Panth KM;van den Beucken T;Biemans R;Lieuwes NG;Weber M;Losen M;Yaromina A;Dubois LJ;Lambin P
基质金属蛋白酶-2 (MMP2) 在肿瘤发生、血管生成和肿瘤侵袭中发挥重要作用。在这项研究中，我们研究了靶向人 MMP2 催化结构域的 Cy5 标记的小免疫蛋白 (aMMP2-SIP) 是否能够非侵入性地检测肿瘤中的 MMP2。为此，我们生成了表达 MMP2（空载体 EV）和敲低（KD）的 HT1080、U373 和 U87 细胞，将其皮下注射到 NMRI-nu 小鼠的侧腹。在注射 Cy5 标记的 aMMP2-SIP 后 0.5、2、4、8、24 和 48 小时 (h.p.i.) 进行光学成像 (Optix MX2)，表明在 24 小时 (P =0.0090) 和 48 小时后，肿瘤与背景的比率显着降低。 (P < 0.0001) U87 MMP2-KD 与对照肿瘤相比。 HT1080 和 U373 型号没有发现差异。根据肿瘤切片和裂解物中的明胶酶谱测定，U87 MMP2-KD 肿瘤的 MMP2 活性显着低于 EV 肿瘤（P<0.0001），而在 HT1080 和 U373 中，EV 和 MMP2-KD 之间没有观察到差异。与这些数据一致，与对照肿瘤相比，仅 U87 MMP2-KD 肿瘤的肿瘤生长减少 (P = 0.0053)。 aMMP2-SIP 摄取与 MMP2 活性相关，因此可能是评估肿瘤中 MMP2 活性的潜在非侵入性成像生物标志物。
Matrix metalloproteinase-2 (MMP2) is important in tumorigenesis, angiogenesis and tumor invasion. In this study, we investigated if the Cy5-tagged small immuno protein targeting the catalytic domain of human MMP2 (aMMP2-SIP) detects MMP2 in tumors non-invasively. For this purpose, we generated MMP2 expressing (empty vector EV) and knock-down (KD) HT1080, U373 and U87 cells, which were injected subcutaneously in the lateral flank of NMRI-nu mice. Optical imaging (Optix MX2) performed at 0.5, 2, 4, 8, 24 and 48 hour post injection (h.p.i.) of Cy5 tagged aMMP2-SIP, indicated significantly lower tumor to background ratios at both 24 (P = 0.0090) and 48 h.p.i. (P < 0.0001) for the U87 MMP2-KD compared to control tumors. No differences were found for HT1080 and U373 models. U87 MMP2-KD tumors had significantly lower MMP2 activity (P < 0.0001) than EV tumors as determined by gelatin zymography in tumor sections and lysates, while no differences were observed between EV and MMP2-KD in HT1080 and U373. In line with these data, only U87 MMP2-KD tumors had a reduced tumor growth compared to control tumors (P = 0.0053). aMMP2-SIP uptake correlates with MMP2 activity and might therefore be a potential non-invasive imaging biomarker for the evaluation of MMP2 activity in tumors.