Tumorigenicity of IL-1α– and IL-1β–Deficient Fibrosarcoma Cells
| Autor: | Irina Nazarenko, Rachid Marhaba, Eli Reich, Elena Voronov, Mario Vitacolonna, Dagmar Hildebrand, Elena Elter, Mohini Rajasagi, Ron N. Apte, Margot Zöller |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 10, Iss 6, Pp 549-562 (2008) |
| Druh dokumentu: | article |
| ISSN: | 1476-5586 1522-8002 |
| DOI: | 10.1593/neo.08286 |
| Popis: | Analyzing the growth of fibrosarcoma lines derived from IL-1α–, IL-1β–, or IL-1αβ–knockout (−/−) mice in the immunocompetent host revealed that tumor-derived IL-1α and IL-1β exert strong and opposing effects on immune response induction, which prohibited the evaluation of a potential impact on tumorigenicity. Therefore, in vivo growth of IL-1–deficient tumor lines was evaluated in nu/nu mice and was compared with in vitro growth characteristics. All IL-1–deficient fibrosarcoma lines grow in immunocompromised mice. However, IL-1α−/−β–competent (comp) lines grow more aggressively, efficiently induce angiogenesis, and recruit inflammatory cells. Despite stronger tumorigenicity of IL-1βcomp lines, IL-1α strengthens anchorage-independent growth, but both IL-1α and IL-1β support drug resistance. Corresponding to the aggressive growth, IL-1βcomp cells display increased matrix adhesion, motility, and cable formation on matrigel, likely supported by elevated αv/β3 and matrix metalloproteinase expression. Recruitment of myeloid cells requires IL-1β but is regulated by IL-1α, because inflammatory chemokine and cytokine expression is stronger in IL-1α−/−βcomp than in IL-1wt lines. This regulatory effect of tumorderived IL-1α is restricted to the tumor environment and does not affect systemic inflammatory response induction by tumor-derived IL-1β. Both sarcoma cell–derived IL-1α and IL-1β promote tumor growth. However, IL-1α exerts regulatory activity on the tumor cell–matrix cross-talk, and only IL-1β initiates systemic inflammation. |
| Databáze: | Directory of Open Access Journals |
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