Establishment of a novel myeloma cell line KPMM2 carrying t(3;14)(q21;q32), which proliferates specifically in response to interleukin-6 through an autocrine mechanism.
We established a new human myeloma cell line, KPMM2, which proliferates specifically in response to IL-6 via an autocrine mechanism. The proliferative response of KPMM2 cells to exogenous IL-6 was significantly stimulated in a dose-dependent manner. The growth was markedly inhibited by an anti-IL-6 mAb and an anti-IL-6 receptor (IL-6R) mAb in a dose-dependent manner. KPMM2 cells expressed IL-6 and IL-6R mRNA by RT-PCR. Flow cytometric analysis showed cell surface expression of IL-6R. IL-6 protein was detected in the culture supernatant by ELISA. IL-11, oncostatin M and leukemia inhibitory factor had no effect on the proliferation of KPMM2 cells although interferon-alpha and interferon-gamma inhibited the growth. Furthermore, KPMM2 cells bore a t(3;14)(q21;q32) translocation and this finding is of potential interest for future studies in the light of the nuclear protein BM28 (CDCL1, for cdc-like 1) mapped on 3q21, which plays an important role in the cell cycle. In this report, we demonstrated completely an IL-6-dependent autocrine growth mechanism in KPMM2 cell line. This cell line may be useful to investigate the pathogenesis of multiple myeloma and to evaluate the therapeutic potential of IL-6 blocking agents in vitro and in vivo.
Goto
H
H
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Shimazaki
C
C
Tatsumi
T
T
Yamagata
N
N
Fujita
N
N
Tsuchiya
M
M
Koishihara
Y
Y
Ohsugi
Y
Y
Nakagawa
M
M
D000368:Aged; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002883:Chromosomes, Human, Pair 14; D002893:Chromosomes, Human, Pair 3; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D016207:Cytokines; D017931:DNA Primers; D015850:Interleukin-6; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6