TMTP1, a novel tumor-homing peptide, specifically targets hematological malignancies and their metastases.

Abstract

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 malignant in situ and 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-cultured 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 measured in vivo by 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.

• Authors: Min Xiao, Zhenya Hong, Lishi Sun, Ying Wu, Na Zhang, Yanan Liu, Danfeng Luo, Jianfeng Zhou, Chunrui Li
• Journal: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 31 Issue 5 Pg. 608 (Oct 2011) ISSN: 1672-0733 [Print] China
• PMID: 22038348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Oligopeptides
• asparagyl-valyl-valyl-arginyl-glutamine

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Drug Delivery Systems
• Female
• HL-60 Cells
• Hematologic Neoplasms (diagnosis, drug therapy, metabolism, pathology)
• Humans
• K562 Cells
• Lymphoma (drug therapy, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Metastasis (diagnosis, drug therapy)
• Oligopeptides (administration & dosage, metabolism)