Montemagno Christopher, Dumas Laurent, Cavaillès Pierre, Ahmadi Mitra, Bacot Sandrine, Debiossat Marlène, Soubies Audrey, Djaïleb Loic, Leenhardt Julien, Leiris Nicolas de, Dufies Maeva, Pagès Gilles, Hernot Sophie, Devoogdt Nick, Perret Pascale, Riou Laurent, Fagret Daniel, Ghezzi Catherine, Broisat Alexis
Laboratory of Bioclinical Radiopharmaceutics, Universite Grenoble Alpes, Inserm, CHU Grenoble Alpes, LRB, 38000 Grenoble, France.
Advanced Accelator Applications, 01630 Saint-Genis-Pouilly, France.
Cancers (Basel). 2019 Jul 23;11(7):1039. doi: 10.3390/cancers11071039.
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 Tc-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, Tc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 ( < 0.01), and 4-fold higher than that of the irrelevant control ( < 0.01). Moreover, Tc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of Tc-Ctl ( < 0.05). Tc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.
乳腺癌研究的最新进展已导致血管细胞黏附分子-1（VCAM-1）被确定为转移定植的关键因素。VCAM-1促进肺转移，并与三阴性乳腺癌（TNBC）的临床早期复发和不良预后相关。我们的目标是在TNBC小鼠模型中对VCAM-1进行体内成像。分析癌症基因组图谱（TCGA）数据库以评估VCAM-1在TNBC中的预后作用。将MDA-MB-231（VCAM-1阳性）和对照HCC70（VCAM-1阴性）TNBC细胞皮下异种移植到小鼠体内，并使用锝标记的抗VCAM-1单克隆抗体（Tc-cAbVCAM1-5）通过单光子发射计算机断层扫描（SPECT）成像在体内评估VCAM-1的表达。然后，将MDA-MB-231细胞静脉注射到小鼠体内，并在8周后通过SPECT成像评估肺转移灶中VCAM-1的表达。TCGA分析表明，VCAM-1与TNBC患者的不良预后相关。在皮下肿瘤模型中，MDA-MB-231中Tc-cAbVCAM1-5的摄取量比HCC70高2倍（<0.01），比无关对照高4倍（<0.01）。此外，MDA-MB-231肺转移灶中Tc-cAbVCAM1-5的摄取量也高于Tc-Ctl（<0.05）。因此，Tc-cAbVCAM1-5是评估VCAM-1作为TNBC肿瘤侵袭性标志物作用的合适工具。
