TMTP1, a Novel Tumor-homing Peptide, Specifically Targets Hematological Malignancies and Their Metastases
TMTP1, a Novel Tumor-homing Peptide, Specifically Targets Hematological Malignancies and Their Metastases
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TMTP1 是一种新型肿瘤归巢肽，专门针对血液恶性肿瘤及其转移
DOI：
10.1007/s11596-011-0569-y
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发表时间：
2011-10-01
影响因子：
--
通讯作者：
Li, Chunrui
中科院分区：
文献类型：
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作者：
Xiao, Min;Hong, Zhenya;Li, Chunrui
TMTP1是我们以往研究中利用鞭毛肽库筛选得到的一种5氨基酸NVVRQ多肽，可用于标记肿瘤状况和转移灶，甚至微转移。在这项研究中，评估了TMTP1特异性靶向恶性造血细胞和血液系统恶性肿瘤转移灶的能力。化学合成FITC-TMTP1。免疫荧光法和竞争试验检测TMTPl与恶性血液病细胞系HL60、K562、SHI-1、Jurkat、Raji、EL-4和脐血单个核细胞的特异性结合能力。从健康人和慢性粒细胞白血病患者的骨髓中分离单个核细胞。用TMTP1或杂交肽与细胞共培养，流式细胞术分析TMTP1肽与恶性血液病原代细胞的结合和亲和力。在EL-4淋巴瘤荷瘤小鼠体内静脉注射FITC标记的TMTP1，检测TMTP1与靶向血液系统恶性肿瘤的结合特异性。结果表明，TMTP1能与HL60、K562、Jurkat、Raji、EL-4和慢性粒细胞白血病原代细胞特异性结合，但不能与正常人骨髓单个核细胞结合。相反，TMTP1可以与来自EL-4细胞系的淋巴瘤转移灶结合，而杂交肽则不能。此外，通过检测FITC-TMTP1可以识别隐匿性转移，具有很高的特异性。提示TMTP1作为一种新的肿瘤归巢多肽，可作为原发恶性肿瘤和转移灶的标志物，用于血液系统恶性肿瘤的早期诊断和抗癌药物的载体治疗。
TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignantin situand metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El–4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding specificity of TMTP1 to target hematological malignancies was measuredin vivoby intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifically bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji, El–4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.