|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1992 : ¥1,400,000 (Direct Cost : ¥1,400,000)
The expression and function of apoptosis-related antigens, adhesion receptors, cytokines and oncogenes were studied in relation to the apoptotic cell death of multiple myeloma cells.
1)Fas antigen was expressed on 4 out of 18 cases of fresh myeloma cells. BCL-2 antigen was expressed in 95%(19/20)of cases. IMN3.1 antigen was not detected in any fresh myeloma cells. Anti-Fas antibody did not significantly induce apoptotic cell death in fresh cells.
2)In multiple myeloma cell lines, 6 out of 11 cell lines expressed Fas antigen. Among those only one cell line, ILKM3, showed apoptosis after treatment with anti-Fas antibody. Apoptosis was documented by the studies utilizing electron microscopy and DNA analysis. The comparison of the expression of apoptosis-related antigens, adhesion receptors, cytokines and oncogenes between ILKM3 and other non-apoptosis-prone cells, suggested that apoptosis-prone cells expressed Fas and IMN3.1 antigens, overexpressed MYC mRNA and scaresely expressed BCL-2 protein.
3)Fresh myeloma cells and myeloma cell lines almost equally expressed adhesion receptors. CD49d, CD58, CD54, CD56 and CD44 were expressed in almost all the cells and cell lines. CD49e, CE49f, CD11a, SLe-x, LAM-1 CD41 and CD51 were expressed in low percentages. Anti-beta 1 integrin antibodies neither completely inhibited adhesion to bone marrow stromal cells nor induced significant apoptosis. Other adhesion receptors in addition to beta 1-integrin were thought to play another key role in the adherence to stromal cells and apoptosis.
4)A newly established cell line, ILKM10, showed stromal cell-dependent growh. Stromal cell-dependent growth was not substituted by IL-6. Treatment by anti-beta 1 integrin antibodies did not induce apoptosis. ILKM10 appears to be the best cell line for the analysis of new cytokines, which regulate the growth and apoptosis in myeloma cells.