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. Author manuscript; available in PMC: 2010 Mar 22.
Published in final edited form as: Cell. 2000 Oct 27;103(3):481–490. doi: 10.1016/s0092-8674(00)00139-2

Figure 2. HPV16/MMP-9 –/– Mice Develop Fewer, but More Malignant, SCCs.

Figure 2

(A) Percentage of SCC-free transgenic mice in three cohorts: HPV16/MMP-9 +/+, n = 133 (FVB/n N14-N20; yellow triangles), HPV16/MMP-9 +/–, n = 76 (FVB/n N4; pink squares), and HPV16/MMP-9 –/–, n = 137 (FVB/n N4; blue diamonds). Both HPV16/MMP-9 +/+ and HPV16/MMP-9 +/– mice exhibit an overall SCC incidence of ~50% (50% and 47% respectively). In contrast, the incidence of SCCs in HPV16/MMP-9 –/– mice was reduced, to ~25% (Fisher's Exact Test, p = 0.0004).

(B) Immunostaining of intermediate filaments (brown staining) reveals degree of keratinocyte differentiation retained in various grades of SCC. Well-differentiated Grade I SCCs exhibit hallmark keratin pearl structures (asterisks) and express the suprabasal keratin K10 while not expressing the simple keratin K8. Grade II SCCs appear less differentiated and express both K10 and K8. In contrast, poorly differentiated Grade III SCCs lose terminal differentiation capacity, do not express K10, while maintaining expression of K8. Grade IV SCCs attain a spindle cell morphology, exhibit limited K10 expression and primarily express the mesenchymal intermediate filament protein, vimentin. Bar: 50 μm.

(C) A shift in tumor grade in MMP-9 –/– mice. SCCs were collected from the three cohorts of mice shown in panel (A) (HPV16/MMP-9 +/+, 133 mice, 67 mice with invasive SCCs, 80 SCCs total; HPV16/MMP-9 +/–, 76 mice, 35 mice with invasive SCCs, 43 SCCs total; HPV16/MMP-9 –/–, 137 mice, 37 mice with invasive SCCs, 42 SCCs total) and graded based on the criteria in panel (B). Both MMP-9-sufficient/HPV16 (+/+ and +/–) cohorts exhibited a similar spectrum of SCC grades, with no incidence of Grade IV SCCs. In contrast, MMP-9-deficient (–/–) transgenic mice exhibited an altered spectrum of SCCs biased toward less differentiated, more malignant cancers (p < 0.0001, Wilcoxon Score for Variable Grade).