A Distinct Macrophage Population Mediates Metastatic Breast Cancer Cell Extravasation, Establishment and Growth
Figure 7
Tumor-macrophage interactions promotes tumor cell extravasation and correlates with initial tumor growth.
(A) Average area of direct interaction between tumor cells and macrophages per tumor cluster measured by confocal microscopy at different time points after iv injection. Statistically different from 5 min time point *p<0.05, **P<0.01 and ***p<0.001 (B) Left four histograms: Average number of macrophages that directly interact with each tumor cell cluster at different time points after iv injection. Statistically different from the 5 min control *p<0.05, **P<0.01. Right three histograms: Interactions following macrophage depletion using Liposome-Clodronate administered 16 hrs before and 2 hours after iv injection as described in the materials and methods. All time points are significantly lower than the macrophage replete mice. (C) Tumor cell extravasation status at different time points after iv injection showing the percentage of totally intravascular (red), extravasating (blue, inside vessels and outside) and extravascular (yellow, completely outside vessels) in normal or macrophage depleted mice using Liposome-Clodronate as described above. Note that data is represented as a percentage of total cells although the number of viable tumor cells is greatly reduced after macrophage depletion (Fig. 2A). The delay in extravasation at 24 hrs following macrophage depletion is statistically significant with p<0.05. (D) Correlation between tumor cluster volume and tumor-macrophage interaction area at 72 hours after tumor cell tail vein injection. p<0.0001, R2 = 0.58 (A–C are based upon 3D images of 10–20 clusters per animal, 3–6 mice per time point. Data are shown as mean+SEM. D., 51 tumor clusters from 3 mice).