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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 6. MMP-9 from Bone Marrow-Derived Cells Is Sufficient to Restore Wild-Type Neoplastic Phenotype in HPV16/MMP-9 –/– Mice.

Figure 6

(A) Percentage of PCNA-positive keratinocytes present in Grade I and/or Grade II SCCs from nonirradiated, nontransplanted, HPV16/MMP-9 +/+ and –/– mice, and from HPV16/MMP-9 +/– and –/– mice that were lethally irradiated and transplanted with either wild-type (+/+) or MMP-9-deficient (–/–) BM-d cells. PCNA-positive keratinocytes were counted from a minimum of five high power (40×) fields/tumor analyzed. Results shown are derived from 5 SCCs each from nonirradiated, nontransplanted HPV16/MMP-9 +/– [46.6% ± 1.9] and –/– [32.3% ± 2.3] mice, 5 SCCs from irradiated/transplanted HPV16/MMP-9 +/–, BMT +/+ [45.6% ± 5.0] and HPV16/MMP-9 –/–, BMT –/– [45.9% ± 4.6] mice, and from the 1 SCC-bearing HPV16/MMP-9 –/–, BMT –/– [29.9% ± 5.1] mouse (p < 0.05, ANOVA [one-way analysis of variance]). Results are shown as mean percentages, ± standard error of the mean.

(B) Keratinocyte proliferation, as measured by immunoreactivity for proliferating cell nuclear antigen (PCNA), in Grade II SCCs from four cohorts of mice: (a) HPV16/MMP-9 +/– (b) HPV16/MMP-9 –/–, (c) HPV16/MMP-9 –/–, irradiated and transplanted with MMP-9 +/+ BM-d cells, and (d) HPV16/MMP-9 –/–, irradiated and transplanted with MMP-9 –/– BM-d cells. Note in (a) that proliferation is heterogeneous throughout the malignant clusters, whereas in (b), proliferation is restricted to within 3–4 cell layers proximal to stroma (s). Transplantation of MMP-9 +/+ BM-d cells restores the characteristic pattern of proliferation to keratinocytes (c). Bar: 100 μm (a–d).

(C) Incidence of SCCs in animals from BMT study (HPV16/MMP-9 +/–, BMT +/+,n = 10 mice, 7 with SCCs; HPV16/MMP-9 –/–, BMT +/+, n = 10 mice, 5 with SCCs; HPV16/MMP-9 –/–, BMT –/–, n = 11 mice, 1 with an SCC) was determined in comparison to nonirradiated, nontransplanted transgenic animals (HPV16/MMP-9 +/+, n = 133, 67 mice with SCCs; HPV16/MMP-9 –/–, n = 137 mice, 37 with SCC).