Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.
Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.
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DOI：
10.7150/thno.7323
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发表时间：
2014
期刊：
影响因子：
12.4
通讯作者：
VanBrocklin HF
中科院分区：
文献类型：
--
作者：
LeBeau AM;Sevillano N;King ML;Duriseti S;Murphy ST;Craik CS;Murphy LL;VanBrocklin HF
亚型靶向治疗可以对改善乳腺癌妇女的生活质量和数量产生巨大影响。尽管最初的治疗反应，癌症复发和获得性耐药性是司空见惯的。迫切需要能够识别耐药病变的非侵入性成像探针，以帮助开发新药和有效利用乳腺癌的现有疗法。蛋白酶受体尿激酶纤溶酶原激活物受体（uPAR）是一种可用于非侵入性成像的靶点。uPAR的表达与表型侵袭性乳腺癌和获得性耐药有关。在来自两种不同乳腺癌亚型的细胞系中对获得性耐药性进行建模，所述两种不同乳腺癌亚型为uPAR阴性管腔A亚型和uPAR阳性三阴性亚型细胞系MDA-MB-231。MCF-7细胞，培养耐他莫昔芬（MCF-7 TamR），被发现显着过度表达uPAR相比，父母的细胞系。当通过产生阿霉素和紫杉醇抗性MDA-MB-231细胞（MDA-MB-231 DoxR和MDA-MB-231 TaxR）在三阴性乳腺癌中建立抗性模型时，uPAR表达得以维持。使用拮抗性uPAR抗体2G 10，通过近红外（NIR）光学成像和111 In-单光子发射计算机断层扫描（SPECT）对uPAR进行体内成像。在注射后72小时，111 In-SPECT探针的肿瘤摄取在三种耐药异种移植物中高（> 46%ID/g），并且在uPAR阴性异种移植物中最小。这项临床前研究表明，uPAR可以靶向成像乳腺癌模型的获得性耐药，导致潜在的临床应用。
Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and 111In-single photon emission computed tomography (SPECT). Tumor uptake of the 111In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications.
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影响因子：
50.5
作者：
Andre, F.;Zielinski, C. C.
通讯作者：
Zielinski, C. C.
影响因子：
45.3
作者：
Gutierrez, MC;Detre, S;Dowsett, M
通讯作者：
Dowsett, M
影响因子：
4.8
作者：
Duriseti, Sai;Goetz, David H.;Craik, Charles S.
通讯作者：
Craik, Charles S.
EMT，癌症干细胞和耐药性：癌症战争中新兴的邪恶轴。
影响因子：
8
作者：
Singh, A.;Settleman, J.
通讯作者：
Settleman, J.
DOI：
10.1073/pnas.1218694110
发表时间：
2013-01-02
影响因子：
11.1
作者：
LeBeau, Aaron M.;Lee, Minhee;Craik, Charles S.
通讯作者：
Craik, Charles S.