CXCL12-secreting and -scavenging cell numbers in the tumor microenvironment influence gradient direction and magnitude.

A, Maximum CXCL12-α (left), -β (center), and -γ (right) gradients over a 24-h period illustrate that gradients are dependent upon cellular makeup. The * and ~ show the strongest gradients into the blood and into the tissue, respectively, and correspond to the same symbols in B. Gradient magnitudes were averaged over 5 runs to account for potential variation in the randomization of cell placement in the model. In all simulations, 200 endothelial CXCR7+ cells were present. White squares designate a gradient of exactly 0. B, Time-series of CXCL12 gradients demonstrate that gradients fluctuate according to circadian rhythm. Dotted lines represent the minimum gradient (0.002 nM/μm) that we determined to be necessary to trigger significant cell migration in a previous work [21]. CT 24 corresponds to 9 pm while CT 12 corresponds to 9 am. Positive gradients correspond to higher CXCL12 tissue concentrations while negative gradients correspond to higher CXCL12 concentrations in the blood. C, Circadian fluctuations of all combinations of CXCL12-secreting and -scavenging cells shown in A.