Article Figures & Data
Figures
- Fig. 1.
Analysis of spontaneous pulmonary metastases in fibrinogen-deficient mice. Representative examples of spontaneous pulmonary metastatic foci produced 12 days after surgical resection of ∼500 mg s.c. LLC tumors in control (A) and fibrinogen-deficient (B) mice. Fibrinogen-deficient mice had significantly fewer pulmonary metastases relative to control animals regardless of whether surgical resection (C) or irradiation (D) was used to control the primary tumor. The horizontal bars represent median values. Ps were generated with the Mann-Whitney U test, two-tailed.
- Fig. 2.
Fibrinogen does not alter the size distribution of spontaneous pulmonary metastatic foci. Scatter plot of the size distribution of individual metastatic foci produced after surgical resection of s.c. transplanted LLC tumors. The arbitrary units from 1–4 used to score the size of metastatic foci are defined as follows: 1 ≤ 0.5 mm; 2 = 0.6–0.9 mm; 3 = 1–1.4 mm; and 4 ≥ 1.5 mm. Ps were generated using the Mann-Whitney U test, two-tailed.
- Fig. 3.
Fibrinogen deficiency diminishes spontaneous pulmonary micrometastases. LLCGFP cells (2.5 × 105) were transplanted into the dorsal subcutis of Fib+ (A) and Fib− (B) mice. The mice were sacrificed 13 days later (s.c. tumors, ∼750 mg), and fluorescent pulmonary micrometastases were visualized using a fluorescence-equipped stereomicroscope. The white bars represent 500 μm. Fibrinogen deficiency resulted in a significant diminution in the number of fluorescent micrometastases visualized/high-powered field (C). The horizontal bars represent median values. Ps were generated with the Mann Whitney U test, two-tailed.
- Fig. 4.
Histological appearance of primary tumors in fibrinogen-deficient mice. A series of five tumors, 300–400 mg in size, from mice of both genotypes was paraffin embedded and sectioned. Representative images are shown. No genotype-dependent differences in overall tumor architecture were observed based on H&E stains of primary LLC tumors from control (A) and fibrinogen-deficient (B) mice. The overlying dermis is labeled with arrows. Tumors grew as dense cellular masses with small, focal areas of necrosis (∗) regardless of genotype. Individual tumor cells demonstrated highly anaplastic features and frequent mitoses in mice of both genotypes. Immunohistological staining for the endothelial cell marker PECAM (brown staining) demonstrated robust tumor angiogenesis in both fibrinogen-deficient (D) and control (C) mice. Furthermore, peritumoral lymphatics, highlighted by immunostaining for LYVE-1 (red), were evident and qualitatively similar in density in fibrinogen-deficient (F) and control (E) mice within the s.c. tissue overlying the tumor mass. The arrow in E highlights a prominent red cell-containing blood vessel that is not stained by the LYVE-1 antibody.
Tables
- Table 1
Effect of fibrinogen deficiency on regional lymphatic metastasis of LLCa
Genotype Total (n) Presence of lymphatic metastases One node Two nodes Three nodes Fib+ 41 27 (66%) 12 (29%) 9 (22%) 6 (15%) Fib− 26 9 (35%) 7 (26%) 2 (8%) 0 -
a P < 0.007; nonparametric analysis (Mann Whitney U test) comparing the total number of positive nodes in all mice of each genotype.
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Volume 62, Issue 23
