Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas.
Human B cell stimulatory factor 2 (BSF-2) was originally characterized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (Mr) 26,000 similar or identical to interferon beta 2, hybridoma plasmacytoma growth factor and hepatocyte stimulating factor. IL-6 has been proposed as a name for this molecule. It is now known that BSF-2 has a wide variety of biological functions and that its target cells are not restricted to normal B cells. Responses are also seen in T cells, plasmacytomas, hepatocytes, haematopoietic stem cells, fibroblasts and rat phoeochromocytoma, PC12 (Satoh, T. et al., manuscript in preparation). Of particular interest to this report is that human BSF-2 is a potent growth factor for murine plasmacytomas and hybridomas. This observation suggested to us that constitutive expression of BSF-2 or its receptor could be responsible for the generation of human myelomas. In this study we report that myeloma cells freshly isolated from patients produce BSF-2 and express its receptors. Moreover, anti-BSF-2 antibody inhibits the in vitro growth of myeloma cells. This is direct evidence that an autocrine loop is operating in oncogenesis of human myelomas.
Kawano
M
M
Department of Internal Medicine, Hiroshima University, Japan.
Hirano
T
T
Matsuda
T
T
Taga
T
T
Horii
Y
Y
Iwato
K
K
Asaoku
H
H
Tang
B
B
Tanabe
O
O
Tanaka
H
H
D000906:Antibodies / Q000502:physiology; D002455:Cell Division; D006133:Growth Substances; D006801:Humans; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D009101:Multiple Myeloma / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D006133:Growth Substances; D015850:Interleukin-6; D007378:Interleukins; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins