Expression of Fas/Apo-1 (CD95) and apoptosis in tumor cells from patients with plasma cell disorders.
Fas/Apo-1 antigen (CD95) is a cell surface molecule that directly mediates apoptosis. Fas expression was studied in five plasma cell lines, 11 multiple myeloma cases, and three plasma cell leukemia (PCL) cases. Induction of apoptosis by anti-Fas antibody was studied in five plasma cell lines and fresh plasma cells from eight patients. Apoptosis was confirmed by morphologic analysis alone or in combination with DNA electrophoresis analysis. Four of the five cell lines showed Fas expression, three of which showed induction of apoptosis by anti-Fas antibody. One cell line, RPMI 8226, showed the highest sensitivity for Fas-mediated apoptosis. High bcl-2 expression was found in KMS12PE, which showed resistance to Fas-mediated apoptosis despite its Fas expression. Plasma cells from seven fresh cases, including all five cases with high serum lactate dehydrogenase (LDH), showed expression of Fas antigen. Fas-induced apoptosis was found in five cases at various levels, although significant induction of apoptosis was found in only one case. Interestingly, Fas-independent apoptosis was induced during culture without anti-Fas antibody in cases with high serum LDH. These results indicate that plasma cells from aggressive myeloma with high LDH express Fas antigen and undergo apoptosis through either Fas-mediated or Fas-independent pathways. An understanding of the mechanism of apoptosis in malignant plasma cells should contribute to investigations of the pathophysiology of and therapy for myeloma/PCL.
Hata
H
H
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Matsuzaki
H
H
Takeya
M
M
Yoshida
M
M
Sonoki
T
T
Nagasaki
A
A
Kuribayashi
N
N
Kawano
F
F
Takatsuki
K
K
D000328:Adult; D000368:Aged; D000906:Antibodies; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D007952:Leukemia, Plasma Cell / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010996:Pleural Effusion; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D012044:Regression Analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis; D019014:fas Receptor
D000906:Antibodies; D000954:Antigens, Surface; D004273:DNA, Neoplasm; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor