title: The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing.
abstract: OBJECTIVE
  Exposing human tumor cells to sublethal doses of external beam radiation up-regulates expression of tumor antigen and accessory molecules, rendering tumor cells more susceptible to killing by antigen-specific CTLs. This study explored the possibility that exposure to palliative doses of a radiopharmaceutical agent could alter the phenotype of tumor cells to render them more susceptible to T cell-mediated killing.
  
  
  METHODS
  Here, 10 human tumor cell lines (4 prostate, 2 breast, and 4 lung) were exposed to increasing doses of the radiopharmaceutical samarium-153-ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP) used in cancer patients to treat pain due to bone metastasis. Fluorescence-activated cell sorting analysis and quantitative real-time PCR analysis for expression of five surface molecules and several tumor-associated antigens involved in prostate cancer were done. LNCaP human prostate cancer cells were exposed to (153)Sm-EDTMP and incubated with tumor-associated antigen-specific CTL in a CTL killing assay to determine whether exposure to (153)Sm-EDTMP rendered LNCaP cells more susceptible to T cell-mediated killing.
  
  
  RESULTS
  Tumor cells up-regulated the surface molecules Fas (100% of cell lines up-regulated Fas), carcinoembryonic antigen (90%), mucin-1 (60%), MHC class I (50%), and intercellular adhesion molecule-1 (40%) in response to (153)Sm-EDTMP. Quantitative real-time PCR analysis revealed additional up-regulated tumor antigens. Exposure to (153)Sm-EDTMP rendered LNCaP cells more susceptible to killing by CTLs specific for prostate-specific antigen, carcinoembryonic antigen, and mucin-1.
  
  
  CONCLUSIONS
  Doses of (153)Sm-EDTMP equivalent to palliative doses delivered to bone alter the phenotype of tumor cells, suggesting that (153)Sm-EDTMP may work synergistically with immunotherapy to increase the susceptibility of tumor cells to CTL killing.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Mala
authors.initials: M
authors.lastname: Chakraborty
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Wansley
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
authors.forename: Sarah
authors.initials: S
authors.lastname: Yu
authors.forename: Chang H
authors.initials: CH
authors.lastname: Paik
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: Michael D
authors.initials: MD
authors.lastname: Becker
authors.forename: William F
authors.initials: WF
authors.lastname: Goeckeler
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
mesh_terms: D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D002469:Cell Separation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D009942:Organometallic Compounds / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000628:therapy*; D011868:Radioisotopes / Q000494:pharmacology*; D012493:Samarium / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D012493:Samarium; C061972:samarium Sm-153 lexidronam