Enbäck J, Laakkonen P
Molecular Cancer Biology Research Program and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Finland.
Biochem Soc Trans. 2007 Aug;35(Pt 4):780-3. doi: 10.1042/BST0350780.
Each normal organ and pathological condition contains organ- or disease-specific molecular tags on its vasculature that constitute a vascular 'zip code' system. Tissue-selective tumour metastasis may also depend on vascular addresses. We have used phage display peptide libraries to map disease-specific differences in the vasculature. By using this technology, we have isolated several peptides which are targeted specifically to tumour blood vessels, lymphatic vessels and/or tumour cells. Some of the tumour-homing peptides recognize common angiogenesis markers and are capable of binding to several types of tumour, whereas other peptides recognize tumour-type-specific differences. We have also shown that the vasculature of a pre-malignant lesion differs from that of a full-blown tumour and also from the vasculature of the corresponding normal organ. Our peptides have revealed molecules that act as novel biomarkers of this vascular heterogeneity. Interestingly, some of our homing peptides are able to penetrate the target cells. This internalization differs from that of the Tat, penetratins and other related peptides in that our peptides enter the cell in a cell-type-specific manner. These peptides appear to be able to concentrate in the target tissue, making them particularly efficient delivery vectors for the targeting of drugs, other therapeutic moieties and imaging agents.
每个正常器官和病理状况在其脉管系统上都含有器官或疾病特异性分子标签，这些标签构成了一个血管“邮政编码”系统。组织选择性肿瘤转移可能也依赖于血管地址。我们利用噬菌体展示肽库来描绘脉管系统中疾病特异性差异。通过使用这项技术，我们分离出了几种特异性靶向肿瘤血管、淋巴管和/或肿瘤细胞的肽。一些肿瘤归巢肽识别常见的血管生成标志物，并能够与多种类型的肿瘤结合，而其他肽则识别肿瘤类型特异性差异。我们还表明，癌前病变的脉管系统不同于成熟肿瘤的脉管系统，也不同于相应正常器官的脉管系统。我们的肽揭示了一些分子，这些分子可作为这种血管异质性的新型生物标志物。有趣的是，我们的一些归巢肽能够穿透靶细胞。这种内化作用与Tat、穿膜肽及其他相关肽不同，因为我们的肽以细胞类型特异性方式进入细胞。这些肽似乎能够在靶组织中富集，使其成为用于靶向药物、其他治疗部分及成像剂的特别有效的递送载体。
