Figure 2. Mmp13 mRNA is expressed by a subset of α-smooth muscle actin positive carcinoma-associated fibroblasts.

MMTV-PyMT tumors from 13-week-old mice were processed for in situ hybridization for Mmp13 (a–e, i–l), Mmp2 (g), and Mmp14 (h). For clarity the hybridization signals (silver grains) are shown with dark-field illumination in b, d, f, g, and h. (c) and (d) are higher magnification of the area with grade III invasive carcinoma framed in (a) and (b). Mmp13 mRNA signal is seen in the areas with grade III invasive carcinoma (c–d, arrows), but not in the surrounding areas with grade I and II MIN (indicated by I and II in a and b). Mmp13 mRNA expression is restricted to the tumor core (f, white arrows), whereas Mmp2 (g) and Mmp14 (h) mRNAs are seen also in the tumor periphery (blue arrows, f, g, and h are adjacent sections). Stromal septae with Mmp13 mRNA positive signal (i, arrows) are seen in areas close to necrotic tissue (N). Mmp13 mRNA signal in tumor areas with squamous metaplasia showing keratinized (K) epithelium (j, arrows). Expression of Mmp13 mRNA is seen in α-smooth muscle-actin immunoreactive myofibroblasts (k and l, arrows), in some areas restricted to myofibroblasts in the delicate strands of stromal tissue within the cellular tumor (l, arrows). All sections were counter-stained with haematoxylin and eosin except (k and l) that were stained with haematoxylin only. Bars: a, b: 700 µm; c, d: 100 µm; e–i: 400 µm; j: 200 µm; k, l: 50 µm.