Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients
Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients
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DOI：
10.1073/pnas.1114503108
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发表时间：
2011-11-15
影响因子：
11.1
通讯作者：
Arap, Wadih
中科院分区：
文献类型：
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作者：
Staquicini, Fernanda I.;Cardo-Vila, Marina;Arap, Wadih
在器官之间或受损组织与正常组织之间的血管中差异表达的分子是有吸引力的治疗靶点;然而，它们在人类脉管系统中的鉴定是具有挑战性的。在这里，我们筛选了癌症患者的肽库，以揭示某些血管床共同或特异的配体受体。从活检中回收的2.35 × 10（6）个基序的调查结果显示了非随机分布，表明全身组织靶向是可行的。通过相似性搜索、蛋白质阵列和亲和层析的高通量分析揭示了四种天然配体-受体，其中三种以前未被识别。其中两种在多种组织中共有（整合素α 4/膜联蛋白A4和组织蛋白酶B/载脂蛋白E3），另外两种在正常组织（白色脂肪组织中的抑制素/膜联蛋白A2）或癌症（骨转移中的白细胞/白细胞蛋白酶-3）中具有限制性和特异性分布。这些发现为生物技术和医学应用提供了血管分子标记物。
Molecules differentially expressed in blood vessels among organs or between damaged and normal tissues, are attractive therapy targets; however, their identification within the human vasculature is challenging. Here we screened a peptide library in cancer patients to uncover ligand-receptors common or specific to certain vascular beds. Surveying similar to 2.35 x 10(6) motifs recovered from biopsies yielded a nonrandom distribution, indicating that systemic tissue targeting is feasible. High-throughput analysis by similarity search, protein arrays, and affinity chromatography revealed four native ligand-receptors, three of which were previously unrecognized. Two are shared among multiple tissues (integrin alpha 4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white adipose tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases). These findings provide vascular molecular markers for biotechnology and medical applications.