Defective CD3zeta chain expression in Herpesvirus saimiri (HVS)-derived T-cell lines in gastric adenocarcinoma.
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.
Lopez-Santalla
Mercedes
M
Inmunologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Krishnan
Sandeep
S
Valeri
Anna P
AP
Aguilera-Montilla
Noemi
N
Fisher
Carolyn U
CU
Perez-Blas
Mercedes
M
Gutierrez-Calvo
Alberto
A
Lasa
Inmaculada
I
Granell-Vicent
Javier
J
Tsokos
George C
GC
Martin-Villa
José M
JM
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
D017252:CD3 Complex; D007376:Interleukin-2; D014764:Viral Proteins; D002118:Calcium