Tumorigenicity of IL-1α- and IL-1β-Deficient Fibrosarcoma Cells

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-1β^comp lines, IL-1α strengthens anchorage-independent growth, but both IL-1α and IL-1β support drug resistance. Corresponding to the aggressive growth, IL-1β^comp cells display increased matrix adhesion, motility, and cable formation on matrigel, likely supported by elevated α_v/β₃ and matrix metalloroteinase 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^-/-β^comp than in IL-1^wt lines. This regulatory effect of tumor-derived 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.