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Paracrine rather than autocrine regulation of myeloma-cell growth and
differentiation by interleukin-6
B Klein, XG Zhang, M Jourdan, J Content, F Houssiau, L Aarden, M Piechaczyk and R Bataille
INSERM U291, Zolad, Montpellier, France.
To explore the mechanisms involved in the pathogenesis of human multiple
myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a
B-cell differentiation factor in humans, and a growth factor for rat/mouse
heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay,
we found that two well-documented human myeloma cell lines, RPMI 8226 and
U266, did not secrete IL-6 and did not express RNA messengers for IL-6.
Neutralizing antibodies to IL-6 did not inhibit their proliferation, and
recombinant IL-6 did not stimulate it. Taken together, these data show that
IL-6 is not the autocrine growth factor of these human myeloma cell lines.
A high production of IL-6 was found in the bone marrows of patients with
fulminating MM, compared with patients with inactive or slightly active MM,
or to healthy donors. This IL-6 production was assigned to adherent cells
of the bone-marrow environment but not to myeloma cells. A spontaneous
proliferation of myeloma cells freshly isolated from patients was observed
in short-term cultures. Recombinant IL-6 was able to amplify it two- to
threefold. The spontaneous proliferation of the myeloma cells was inhibited
by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3
weeks of culture, the myeloma-cell proliferation progressively declined and
no IL-6-dependent myeloma cell lines could be obtained despite repeated
additions of fresh IL-6 and costimulation with other cytokines such as
tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a
paracrine but not autocrine regulation of the growth and differentiation of
myeloma cells by IL-6.
Volume 73,
Issue 2,
pp. 517-526,
02/01/1989
Copyright © 1989 by The American Society of Hematology
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|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
|
|
M. Trikha, R. Corringham, B. Klein, and J.-F. Rossi
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[Full Text]
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|
|
|
|
|
|
|
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101(12):
4667 - 4679.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Gojo, B. Zhang, and R. G. Fenton
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Lin, K. Podar, D. Gupta, Y.-T. Tai, S. Li, E. Weller, T. Hideshima, S. Lentzsch, F. Davies, C. Li, et al.
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62(17):
5019 - 5026.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Akiyama, T. Hideshima, T. Hayashi, Y.-T. Tai, C. S. Mitsiades, N. Mitsiades, D. Chauhan, P. Richardson, N. C. Munshi, and K. C. Anderson
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July 1, 2002;
62(13):
3876 - 3882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ratta, F. Fagnoni, A. Curti, R. Vescovini, P. Sansoni, B. Oliviero, M. Fogli, E. Ferri, G. R. Della Cuna, S. Tura, et al.
Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6
Blood,
June 17, 2002;
100(1):
230 - 237.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-T. Brenne, T. Baade Ro, A. Waage, A. Sundan, M. Borset, and H. Hjorth-Hansen
Interleukin-21 is a growth and survival factor for human myeloma cells
Blood,
May 15, 2002;
99(10):
3756 - 3762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Zhang, I. Gojo, and R. G. Fenton
Myeloid cell factor-1 is a critical survival factor for multiple myeloma
Blood,
March 15, 2002;
99(6):
1885 - 1893.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ueda, N. Bruchovsky, and M. D. Sadar
Activation of the Androgen Receptor N-terminal Domain by Interleukin-6 via MAPK and STAT3 Signal Transduction Pathways
J. Biol. Chem.,
February 22, 2002;
277(9):
7076 - 7085.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. De Vos, G. Couderc, K. Tarte, M. Jourdan, G. Requirand, M.-C. Delteil, J.-F. Rossi, N. Mechti, and B. Klein
Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays
Blood,
August 1, 2001;
98(3):
771 - 780.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. S. Shapiro, M. N. Mollenauer, and A. Weiss
Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production: implications for multiple myeloma progression
Blood,
July 1, 2001;
98(1):
187 - 193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Frassanito, A. Cusmai, G. Iodice, and F. Dammacco
Autocrine interleukin-6 production and highly malignant multiple myeloma: relation with resistance to drug-induced apoptosis
Blood,
January 15, 2001;
97(2):
483 - 489.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Tu, A. Gardner, and A. Lichtenstein
The Phosphatidylinositol 3-Kinase/AKT Kinase Pathway in Multiple Myeloma Plasma Cells: Roles in Cytokine-dependent Survival and Proliferative Responses
Cancer Res.,
December 1, 2000;
60(23):
6763 - 6770.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. C. Rawstron, J. A. L. Fenton, J. Ashcroft, A. English, R. A. Jones, S. J. Richards, G. Pratt, R. Owen, F. E. Davies, J. A. Child, et al.
The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells
Blood,
December 1, 2000;
96(12):
3880 - 3886.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
