Figure 9. Cdc42 overexpressing fibroblasts promote tumor growth in vivo. We used a xenograft model employing MDA-MB-231 breast cancer cells injected into the flanks of athymic nude mice. MDA-MB-231 breast cancer cells were co-injected with either the empty vector (Lv-105), SMA- or Cdc42- overexpressing fibroblasts. (A) Comparative trend measurements for tumor growth (days 7–25 post-injection). Tumor volumes were measured with callipers about twice a week and mean tumor volume is plotted vs. time, for each experimental group. (B) Tumor growth. Tumor volumes were also measured at 4 weeks post-injection. Note that fibroblasts overexpressing Cdc42 significantly promote tumor growth, resulting in a 1.75-fold increase in tumor volume. p = 0.01; n = 10 tumors per experimental group. (C) Tumor angiogenesis. Tumor frozen sections were cut and immunostained with anti-CD31 antibodies. Then, vascular density (number of vessels per field) was quantified. The observed 25% increase in tumor angiogenesis in Cdc42 tumors is not sufficient to account for a near 2-fold increase in tumor growth. Instead, metabolic reprogramming of the tumor microenvironment, toward L-lactate production, is a more likely mechanism.