Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH, USA.
Int J Cancer. 2013 Apr 1;132(7):1624-32. doi: 10.1002/ijc.27838. Epub 2012 Oct 11.
Detection of an extracellular cleaved fragment of a cell-cell adhesion molecule represents a new paradigm in molecular recognition and imaging of tumors. We previously demonstrated that probes that recognize the cleaved extracellular domain of receptor protein tyrosine phosphatase mu (PTPmu) label human glioblastoma brain tumor sections and the main tumor mass of intracranial xenograft gliomas. In this article, we examine whether one of these probes, SBK2, can label dispersed glioma cells that are no longer connected to the main tumor mass. Live mice with highly dispersive glioma tumors were injected intravenously with the fluorescent PTPmu probe to test the ability of the probe to label the dispersive glioma cells in vivo. Analysis was performed using a unique three-dimensional (3D) cryo-imaging technique to reveal highly migratory and invasive glioma cell dispersal within the brain and the extent of colabeling by the PTPmu probe. The PTPmu probe labeled the main tumor site and dispersed cells up to 3.5 mm away. The cryo-images of tumors labeled with the PTPmu probe provide a novel, high-resolution view of molecular tumor recognition, with excellent 3D detail regarding the pathways of tumor cell migration. Our data demonstrate that the PTPmu probe recognizes distant tumor cells even in parts of the brain where the blood-brain barrier is likely intact. The PTPmu probe has potential translational significance for recognizing tumor cells to facilitate molecular imaging, a more complete tumor resection and to serve as a molecular targeting agent to deliver chemotherapeutics to the main tumor mass and distant dispersive tumor cells.
检测细胞间黏附分子的细胞外裂解片段代表了分子识别和肿瘤成像的新范例。我们之前证明，识别受体蛋白酪氨酸磷酸酶 μ（PTPmu）裂解细胞外结构域的探针可标记人类脑胶质瘤脑肿瘤切片和颅内异种移植物神经胶质瘤的主要肿瘤块。在本文中，我们研究了这些探针之一 SBK2 是否可以标记不再与主要肿瘤块相连的分散性神经胶质瘤细胞。用荧光 PTPmu 探针静脉内注射具有高度分散性神经胶质瘤肿瘤的活小鼠，以测试探针在体内标记分散性神经胶质瘤细胞的能力。使用独特的三维（3D）冷冻成像技术进行分析，以揭示脑内高度迁移和侵袭性神经胶质瘤细胞的分散以及 PTPmu 探针的标记程度。PTPmu 探针标记了主要肿瘤部位和分散的细胞，距离可达 3.5 毫米。用 PTPmu 探针标记的肿瘤的冷冻图像提供了分子肿瘤识别的新颖、高分辨率视图，具有出色的 3D 细节，可了解肿瘤细胞迁移的途径。我们的数据表明，即使在血脑屏障可能完整的大脑区域，PTPmu 探针也能识别远处的肿瘤细胞。PTPmu 探针具有识别肿瘤细胞的潜在转化意义，有助于分子成像、更完整的肿瘤切除，并作为分子靶向剂将化疗药物输送到主要肿瘤块和远处分散的肿瘤细胞。
