Figure 3. Functional influence of IL-6 and IL-8.

(a,b) The addition of recombinant IL-6 alone or recombinant IL-8 alone do not increase cell speed. (c) The addition of recombinant IL-6 and IL-8 in combination at the precise concentrations found in a matrix containing a high density of 50 cells mm⁻³ (RM) recapitulates the high speed observed of human fibrosarcoma cells at high densities. (d) Decreased speed at LD (ρ=10) where cells are exposed to conditioned medium produced by IL-6 and IL-8 knockdown cells and conditioned medium obtained from a matrix containing a high cell density (HD) following exposure to specific IL-6 and IL-8 functional antibodies compared with control cells exposed to conditioned medium from wild-type cells at HD (ρ=50). (e) Decreased speed of the IL-6 and IL-8 knockdown cells at LD (ρ=10) and HD (ρ=50). (f) The addition of recombinant IL-6 and IL-8 in combination at the precise concentrations found in a matrix containing a high density of 100 cells mm⁻³ recapitulates the high speed observed of human carcinoma cells at high densities. (g) Cartoon depicts the fact that IL-6 and IL-8 are both required to influence cancer cell motility. (h) Decreased speed of the IL-6R and IL-8R knockdown cells at LD (ρ=10) and HD (ρ=50). (i) Cartoon depicts that Tocilizumab and Reparixin can be used to block the cognate receptors of IL-6 and IL-8. (j) Individually, Tocilizumab and Reparixin decreased cell speed of human fibrosarcoma cells embedded in a 3D matrix at LD (ρ=10) and HD (ρ=50) compared with cells exposed to fresh medium (0). (k,l) Tocilizumab and Reparixin in combination greatly decrease cell speed of cells embedded in a 3D matrix at LD (ρ=10) and HD (ρ=50) compared with cells exposed to fresh medium (0). In all panels, data is represented as mean±s.e.m. from three independent experiments. *P<0.05; **P<0.01; ***P<0.001 (ANOVA).