title: TIP-1 translocation onto the cell plasma membrane is a molecular biomarker of tumor response to ionizing radiation.
abstract: BACKGROUND
  Tumor response to treatment has been generally assessed with anatomic and functional imaging. Recent development of in vivo molecular and cellular imaging showed promise in time-efficient assessment of the therapeutic efficacy of a prescribed regimen. Currently, the in vivo molecular imaging is limited with shortage of biomarkers and probes with sound biological relevance. We have previously shown in tumor-bearing mice that a hexapeptide (HVGGSSV) demonstrated potentials as a molecular imaging probe to distinguish the tumors responding to ionizing radiation (IR) and/or tyrosine kinase inhibitor treatment from those of non-responding tumors.
  
  
  RESULTS
  In this study we have studied biological basis of the HVGGSSV peptide binding within the irradiated tumors by use of tumor-bearing mice and cultured cancer cells. The results indicated that Tax interacting protein 1 (TIP-1, also known as Tax1BP3) is a molecular target that enables the selective binding of the HVGGSSV peptide within irradiated xenograft tumors. Optical imaging and immunohistochemical staining indicated that a TIP-1 specific antibody demonstrated similar biodistribution as the peptide in tumor-bearing mice. The TIP-1 antibody blocked the peptide from binding within irradiated tumors. Studies on both of human and mouse lung cancer cells showed that the intracellular TIP-1 relocated to the plasma membrane surface within the first few hours after exposure to IR and before the onset of treatment associated apoptosis and cell death. TIP-1 relocation onto the cell surface is associated with the reduced proliferation and the enhanced susceptibility to the subsequent IR treatment.
  
  
  CONCLUSIONS
  This study by use of tumor-bearing mice and cultured cancer cells suggested that imaging of the radiation-inducible TIP-1 translocation onto the cancer cell surface may predict the tumor responsiveness to radiation in a time-efficient manner and thus tailor radiotherapy of cancer.
authors: Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
authors: Hailun
authors: H
authors: Wang
authors: Heping
authors: H
authors: Yan
authors: Allie
authors: A
authors: Fu
authors: Miaojun
authors: M
authors: Han
authors: Dennis
authors: D
authors: Hallahan
authors: Zhaozhong
authors: Z
authors: Han
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D001667:Binding, Competitive; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism / Q000528:radiation effects; D008780:Methyltransferases; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D054731:PDZ Domains; D021381:Protein Transport / Q000528:radiation effects
chemical_list: D000906:Antibodies; D015415:Biomarkers; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; C421249:TAX1BP3 protein, human; D008780:Methyltransferases; C503312:tension-induced inhibited protein, mouse