title: Defective CD3zeta chain expression in Herpesvirus saimiri (HVS)-derived T-cell lines in gastric adenocarcinoma.
abstract: Low expression of the CD3zeta chain has been reported in patients with cancer and it has been suggested that tumor-derived factors are involved in its downregulation. The expression of CD3zeta chain was measured in T-cell lines from patients with gastric adenocarcinoma and healthy volunteers and grown in vitro for several months and, hence, in the absence of any tumor-derived factors. T-cell lines of mucosal origin were obtained by Herpesvirus saimiri transformation from gastric cancer patients. The expression of CD3zeta and CD3epsilon was measured by flow cytometry and Western-blot analysis. Calcium mobilization and apoptosis rate were also measured. The levels of CD3zeta, but not CD3epsilon, chain on the cell surface were significantly reduced in T-cell lines derived from patients with gastric cancer when cultured in the absence of IL-2. Western-blot analysis of total cell extracts or lipid raft fractions confirmed this finding. Calcium mobilization, a measure of signal transduction, was reduced in T cell lines from patients with gastric cancer. We conclude that T cells from patients with cancer express lower levels of CD3zeta. This downregulation is not caused by a direct effect of tumor-derived factors but, rather, it appears to be inherent to the patient cells. The low CD3zeta expression would render T lymphocytes unable to control the growth of tumor cells.
authors.affiliation: Inmunologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Lopez-Santalla
authors.forename: Sandeep
authors.initials: S
authors.lastname: Krishnan
authors.forename: Anna P
authors.initials: AP
authors.lastname: Valeri
authors.forename: Noemi
authors.initials: N
authors.lastname: Aguilera-Montilla
authors.forename: Carolyn U
authors.initials: CU
authors.lastname: Fisher
authors.forename: Mercedes
authors.initials: M
authors.lastname: Perez-Blas
authors.forename: Alberto
authors.initials: A
authors.lastname: Gutierrez-Calvo
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Lasa
authors.forename: Javier
authors.initials: J
authors.lastname: Granell-Vicent
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
authors.forename: José M
authors.initials: JM
authors.lastname: Martin-Villa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D001483:Base Sequence; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016678:Genome / Q000235:genetics; D006567:Herpesvirus 2, Saimiriine / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D007376:Interleukin-2; D014764:Viral Proteins; D002118:Calcium