In Vivo Assessment of VCAM-1 Expression by SPECT/CT Imaging in Mice Models of Human Triple Negative Breast Cancer

通过 SPECT/CT 成像对人类三阴性乳腺癌小鼠模型中的 VCAM-1 表达进行体内评估

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作者:Christopher Montemagno, Laurent Dumas, Pierre Cavaillès, Mitra Ahmadi, Sandrine Bacot, Marlène Debiossat, Audrey Soubies, Loic Djaïleb, Julien Leenhardt, Nicolas de Leiris, Maeva Dufies, Gilles Pagès, Sophie Hernot, Nick Devoogdt, Pascale Perret, Laurent Riou, Daniel Fagret, Catherine Ghezzi, Alexis

Abstract

Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using 99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, 99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, 99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of 99mTc-Ctl (p < 0.05). 99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.

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