Figure 4. Proposed mechanism.

(a) Principle component analysis (PCA) of the top 930 most significant genes to determine the relationship of global transcriptomes. (b) Heat map demonstrating the difference between gene ontology categories. (c) Table demonstrating gene ontology categories. (d) Activity of STAT3 in 3D conditions at LD (ρ=10) and HD (ρ=50). (e) Decreased cell speed of human fibrosarcoma cells embedded in a 3D matrix exposed to JAK2 inhibitor, AG-490, STAT3 inhibitor, S3I-201, and Arp2/3 complex inhibitor, CK 666, at LD (ρ=10) and HD (ρ=50) compared with cells exposed to fresh medium (0). (f) Increased mRNA expression of ACTR2 at HD. (g) The addition of recombinant IL-6 and IL-8 alone does not increase protrusion frequency, however 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) significantly increases the frequency of cellular protrusions. (h) Increased mRNA expression of WASF3 at HD and cells exposed to 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. (i) Cartoon depiction of the IL-6 and the IL-8 signalling pathway leading to enhanced cell motility. 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).