IL-6 transgenic mouse model for extraosseous plasmacytoma

被引:99
作者
Kovalchuk, AL
Kim, JS
Park, SS
Coleman, AE
Ward, JM
Morse, HC
Kishimoto, T
Potter, M
Janz, S
机构
[1] NCI, Genet Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA
[2] NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA
[3] Korea Res Inst Biosci & Biotechnol, Taejon 305333, South Korea
[4] NCI, Vet & Tumor Pathol Sect, NIH, Ft Detrick, MD 21702 USA
[5] Osaka Univ, Sch Med, Inst Mol & Cellular Biol, Osaka 565, Japan
关键词
D O I
10.1073/pnas.022643999
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Plasma cell neoplasms in humans comprise plasma cell myeloma, otherwise known as multiple myeloma, Ig deposition and heavy chain diseases, and plasmacytoma (PCT). A subset of PCT, designated extramedullary PCT, is distinguished from multiple myeloma and solitary PCT of bone by its distribution among various tissue sites but not the bone marrow. Extramedullary (extraosseus) PCT are rare spontaneous neoplasms of mice but are readily induced in a susceptible strain, BALB/c, by treatment with pristane. The tumors develop in peritoneal granulomas and are characterized by Myc-activating T(12;15) chromosomal translocations and, most frequently, by secretion of IgA. A uniting feature of human and mouse plasma cell neoplasms is the critical role played by IL-6, a B cell growth, differentiation, and survival factor. To directly test the contribution of IL-6 to PCT development, we generated BALB/c mice carrying a widely expressed IL-6 transgene. All mice exhibited lymphoproliferation and plasmacytosis. By 18 months of age, over half developed readily transplantable PCT in lymph nodes, Peyer's patches, and sometimes spleen. These neoplasms also had T(12;15) translocations, but remarkably, none expressed IgA. Unexpectedly, approximate to30% of the mice developed follicular and diffuse large cell B cell lymphomas that often coexisted with PCT. These findings provide a unique model of extramedullary PCT for studies on pathogenesis and treatment and suggest a previously unappreciated role for IL-6 in the genesis of germinal center-derived lymphomas.
引用
收藏
页码:1509 / 1514
页数:6
相关论文
共 43 条
[1]  
Barillé S, 2000, EUR CYTOKINE NETW, V11, P546
[2]   NEUROLOGIC DISEASE INDUCED IN TRANSGENIC MICE BY CEREBRAL OVEREXPRESSION OF INTERLEUKIN-6 [J].
CAMPBELL, IL ;
ABRAHAM, CR ;
MASLIAH, E ;
KEMPER, P ;
INGLIS, JD ;
OLDSTONE, MBA ;
MUCKE, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) :10061-10065
[3]  
CORY S, 1986, ADV CANCER RES, V47, P189, DOI 10.1016/S0065-230X(08)60200-6
[4]   INVITRO CULTURE OF PRIMARY PLASMACYTOMAS REQUIRES STROMAL CELL FEEDER LAYERS [J].
DEGRASSI, A ;
HILBERT, DM ;
RUDIKOFF, S ;
ANDERSON, AO ;
POTTER, M ;
COON, HG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (05) :2060-2064
[5]   ACTIVATION OF THE C-MYC ONCOGENE IN A PRECURSOR-B-CELL BLAST CRISIS OF FOLLICULAR LYMPHOMA, PRESENTING AS COMPOSITE LYMPHOMA [J].
DEJONG, D ;
VOETDIJK, BMH ;
BEVERSTOCK, GC ;
VANOMMEN, GJB ;
WILLEMZE, R ;
KLUIN, PM .
NEW ENGLAND JOURNAL OF MEDICINE, 1988, 318 (21) :1373-1378
[6]   AIRWAY EPITHELIAL-CELL EXPRESSION OF INTERLEUKIN-6 IN TRANSGENIC MICE - UNCOUPLING OF AIRWAY INFLAMMATION AND BRONCHIAL HYPERREACTIVITY [J].
DICOSMO, BF ;
GEBA, GP ;
PICARELLA, D ;
ELIAS, JA ;
RANKIN, JA ;
STRIPP, BR ;
WHITSETT, JA ;
FLAVELL, RA .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (05) :2028-2035
[7]   In situ class switching and differentiation to IgA-producing cells in the gut lamina propria [J].
Fagarasan, S ;
Kinoshita, K ;
Muramatsu, M ;
Ikuta, K ;
Honjo, T .
NATURE, 2001, 413 (6856) :639-643
[8]  
FATTORI E, 1994, BLOOD, V83, P2570
[9]   IL-6 expression in neurons of transgenic mice causes reactive astrocytosis and increase in ramified microglial cells but no neuronal damage [J].
Fattori, E ;
Lazzaro, D ;
Musiani, P ;
Modesti, A ;
Alonzi, T ;
Ciliberto, G .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1995, 7 (12) :2441-2449
[10]   Accelerated appearance of multiple B cell lymphoma types in NFS/N mice congenic for ecotropic murine leukemia viruses [J].
Hartley, JW ;
Chattopadhyay, SK ;
Lander, MR ;
Taddesse-Heath, L ;
Naghashfar, Z ;
Morse, HC ;
Fredrickson, TN .
LABORATORY INVESTIGATION, 2000, 80 (02) :159-169