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Differential effect...
Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness
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Song, XP (författare)
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Dvorkin, T (författare)
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Fima, E (författare)
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Cagnano, E (författare)
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Benharroch, D (författare)
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Shendler, Y (författare)
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- Björkdahl, Olle (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Segal, S (författare)
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Dinarello, CA (författare)
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Apte, RN (författare)
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(creator_code:org_t)
- 2003
- 2003
- Engelska.
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Ingår i: Journal of Immunology. - 1550-6606. ; 171:12, s. 6448-6456
- Relaterad länk:
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http://www.jimmunol....
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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Song, XP
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Dvorkin, T
-
Fima, E
-
Cagnano, E
-
Benharroch, D
-
Shendler, Y
-
visa fler...
-
Björkdahl, Olle
-
Segal, S
-
Dinarello, CA
-
Apte, RN
-
visa färre...
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Lunds universitet