Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment.
The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.
Ishiura
Yoshihito
Y
Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505, Japan.
Kotani
Norihiro
N
Yamashita
Ryusuke
R
Yamamoto
Harumi
H
Kozutsumi
Yasunori
Y
Honke
Koichi
K
D000951:Antigens, Neoplasm / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007518:Isoantibodies / Q000276:immunology / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D018800:Thy-1 Antigens / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D007518:Isoantibodies; D018800:Thy-1 Antigens; C035678:anti-Thy antibody