Figure 1. Changes in stromal organization during tumor progression.

(A) Changes in overall tissue composition with tumor stages in the MMTV-PyMT mouse mammary carcinoma model. Hematoxylin and eosin stained sections (H&E). With tumor progression, the architecture of the carcinoma cells bears less and less resemblance to the architecture of the tissue from which it was derived. The stromal tissue also changes, for example, from a tissue dominated by adipocytes to one dominated by extracellular matrix, fibroblasts and immune cells (adapted from Egeblad et al., 2008; Lin et al., 2003).

(B) Changes in extracellular matrix. Fibrillar collagens are stained with picrosirius red, shown as the birefringent stain under polarized light (arrows); counterstained with hematoxylin. With tumor progression, fibrillar collagen accumulates at the invasive edge of the tumor and surrounding nests of cancer cells (adapted from Levental et al., 2009; Provenzano et al., 2006).

(D) With increasing tumor stage, the tumor vasculature becomes increasingly abnormal, e.g., with dilated vessels. The vasculature is labeled by intravenous injection of FITC-tomato lectin, green (arrows). Nuclei stained with propidium iodide are shown in red. Scale bars: 50 μm (adapted from Lin et al., 2006).

(D) Leukocyte infiltration increases with tumor progression. Immune cells are labeled with antibodies against the common leukocyte marker CD45, green (arrows). Nuclei stained with propidium iodide are shown in blue (adapted from Egeblad et al., 2008).