Figure 4

The tumor-stromal interaction: representation of the three TACS in Wnt-1 mouse tumors. (A-C) Micrographs illustrating the identified TACS. A: TACS-1. MPE/SHG image of TACS-1. Namely, a region of dense collagen (a, and surface map) "above" a non-palpable tumor (b,c; yellow outline) that is indicative of the presence of a small tumor (also see Additional file 5). The surface map quantifies the intensity of the fluorescent signal relative to x-y location, and clearly demonstrates an increased collagen signal, and is representative of six Wnt-1 tumors and eight PyVT tumors (not shown) B: TACS-2. MPE/SHG image of the second TACS indicated by the presence of straightened (taut) fibers characteristic of a larger Wnt-1 tumor. B: a-c, MPE/SHG images of collagen fibers in Wnt-1 mice stretched around a relatively smooth tumor boundary (outlined with a yellow line in c) as demonstrated by the fact that majority of the fibers are parallel to the tumor boundary. B: histogram, the angle of collagen fibers relative to a line tangential to the tumor boundary was measured for 86 regions in six independent tumors, and graphed as a frequency distribution resulting in a distribution of fibers around 0°. C: TACS-3. The third TACS: aligned collagen fibers at regions of cell invasion in Wnt-1 mice. C: a-c, he irregular tumor boundary associated with local invasion is outlined in yellow (in a) and connected to fibers that are primarily distributed normal to the initial tumor boundary, represented by a frequency distribution around 90° relative to the tumor boundary. C: histogram, the angle of collagen fibers relative to a line tangential to the tumor boundary was measured for 71 regions in six independent tumors, and graphed as a frequency distribution resulting in a distribution of fibers near 90°. Scale bars equal 25 μm.