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-TMTP 1 was chemically synthesized.Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPI 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 TMTP 1 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.
ABSTRACT
to the changes of pro-proliferation genes and anti-apoptosis genes.