Source:http://linkedlifedata.com/resource/pubmed/id/14662844
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2003-12-9
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| pubmed:abstractText |
In this study, we show that distinct compartmentalization patterns of the IL-1 molecules (IL-1alpha and IL-1beta), in the milieu of tumor cells that produce them, differentially affect the malignant process. Active forms of IL-1, namely precursor IL-1alpha (pIL-1alpha), mature IL-1beta (mIL-1beta), and mIL-1beta fused to a signal sequence (ssIL-1beta), were transfected into an established fibrosarcoma cell line, and tumorigenicity and antitumor immunity were assessed. Cell lines transfected with pIL-1alpha, which expresses IL-1alpha on the membrane, fail to develop local tumors and activate antitumor effector mechanisms, such as CTLs, NK cells, and high levels of IFN-gamma production. Cells transfected with secretable IL-1beta (mIL-1beta and ssIL-1beta) were more aggressive than wild-type and mock-transfected tumor cells; ssIL-1beta transfectants even exhibited metastatic tumors in the lungs of mice after i.v. inoculation (experimental metastasis). In IL-1beta tumors, increased vascularity patterns were observed. No detectable antitumor effector mechanisms were observed in spleens of mice injected with IL-1beta transfectants, mock-transfected or wild-type fibrosarcoma cells. Moreover, in spleens of mice injected with IL-1beta transfectants, suppression of polyclonal mitogenic responses (proliferation, IFN-gamma and IL-2 production) to Con A was observed, suggesting the development of general anergy. Histologically, infiltrating mononuclear cells penetrating the tumor were seen at pIL-1alpha tumor sites, whereas in mIL-1beta and ssIL-1beta tumor sites such infiltrating cells do not penetrate inside the tumor. This is, to our knowledge, the first report on differential, nonredundant, in vivo effects of IL-1alpha and IL-1beta in malignant processes; IL-1alpha reduces tumorigenicity by inducing antitumor immunity, whereas IL-1beta promotes invasiveness, including tumor angiogenesis, and also induces immune suppression in the host.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0022-1767
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| pubmed:author |
pubmed-author:ApteRon NRN,
pubmed-author:BenharrochDanielD,
pubmed-author:BjorkdahlOlleO,
pubmed-author:CagnanoEmanuelaE,
pubmed-author:DinarelloCharles ACA,
pubmed-author:DvorkinTatyanaT,
pubmed-author:FimaEyalE,
pubmed-author:SegalShragaS,
pubmed-author:ShendlerYaakovY,
pubmed-author:SongXiaopingX,
pubmed-author:VoronovElenaE
|
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
171
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
6448-56
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:14662844-Adjuvants, Immunologic,
pubmed-meshheading:14662844-Animals,
pubmed-meshheading:14662844-Cell Line, Transformed,
pubmed-meshheading:14662844-Cell Line, Tumor,
pubmed-meshheading:14662844-Cell Movement,
pubmed-meshheading:14662844-Cell Transformation, Neoplastic,
pubmed-meshheading:14662844-Cytotoxicity, Immunologic,
pubmed-meshheading:14662844-Female,
pubmed-meshheading:14662844-Fibrosarcoma,
pubmed-meshheading:14662844-Injections, Intravenous,
pubmed-meshheading:14662844-Interleukin-1,
pubmed-meshheading:14662844-Killer Cells, Natural,
pubmed-meshheading:14662844-Leukocytes, Mononuclear,
pubmed-meshheading:14662844-Male,
pubmed-meshheading:14662844-Mice,
pubmed-meshheading:14662844-NIH 3T3 Cells,
pubmed-meshheading:14662844-Neoplasm Invasiveness,
pubmed-meshheading:14662844-Neoplasm Transplantation,
pubmed-meshheading:14662844-Neovascularization, Pathologic,
pubmed-meshheading:14662844-Spleen,
pubmed-meshheading:14662844-Transfection
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness.
|
| pubmed:affiliation |
Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|