Study of TACS-2 and -3 in the more aggressive PyVT mouse tumor model. (A) TACS-2, with an enlarged cutout region (B) shown at higher brightness and contrast levels and a rough demarcation of the tumor-stromal boundary (red line; s = stroma; t = tumor) to further indicate the wrapping of the collagen parallel to the tumor boundary (distribution near 0°, see top right TACS-2 histogram of 106 regions from eight independent tumors). (C) TACS-3, with an enlarged cutout region (D) shown at higher brightness and contrast levels and a rough demarcation of the tumor-stromal boundary (red line; s = stroma; t = tumor). Note that although some cells have moved past this boundary (examples = x) into the fibers, the boundary serves as a general representation of irregular invasive region into radially aligned collagen fibers (frequency distribution around 90°, see middle right TACS-3 histogram of 109 regions from eight independent tumors). Furthermore, analysis of TACS-3 regions (E) at higher magnification (F) show endogenous cells associated with fibers at the tumor-stromal boundary and within the tumor. * Indicates examples of fibers interdigitated with the invasive tumor boundary and in contact with the invading tumor cells (red arrows). Scale bar for MPE/SHG images A, C, E, and F equals 25 μm, and 10 μm for B and D.
Provenzano et al. BMC Medicine 2006 4:38 doi:10.1186/1741-7015-4-38