Table S1. Expression correlation between epidermal growth factor receptor (EGFR) and members of the fibrinolytic system in human cervical cancer samples.
EGFR
r P PLAT (tPA) 0.39 ≤0.0001 PLAUR (uPAR) 0.004 0.9500 LRP1 0.4 ≤0.0001 ANXA2 0.24 ≤0.0001 S100A10 0.24 ≤0.0001 KRT8 (CK-8) –0.42 ≤0.0001
PLAT (tPA): tissue-type plasminogen activator; PLAUR (uPAR): urokinase-type plasminogen activator receptor; LRP1: low-density lipoprotein receptor-related protein 1, S100A10: S100 calcium-binding protein A10; ANXA2: annexin A2; KRT8 (CK-8): cytokeratin-8. n=302.
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Figure S1. Overall survival analysis of patients that had overexpression of individual fibrinolytic system genes. Overall survival analysis of cervical cancer patients with gene expression of 1.5 standard deviations above the median for tPA (A), uPAR (B), LRP1 (C), S100A10 (D), ANXA2 (E), and CK-8 (F) was obtained by employing the tool cBioPortal, taking data from 302 patients deposited on TCGA. Survival curve comparison was done through the Log-rank (Mantel-Cox) statistical test. tPA: tissue-type plasminogen activator; uPAR: urokinase-type plasminogen activator receptor; LRP1: low density lipoprotein receptor-related protein 1; S100A10: S100 calcium-binding protein A10; ANXA2: annexin A2; CK-8: cytokeratin-8.
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Figure S2. Epidermal growth factor receptor (EGFR) signaling does not modulate urokinase-type plasminogen activator (uPA) expression in C-33A cells. A, Real-time PCR of uPA gene expression in C-33A cells treated or not with EGF for 1.5 h. Data are reported as means±SD of three independent experiments. One-sample t-test was used for statistical analysis. B, Representative graph of the plasmin enzymatic activity assay performed on C-33A cells treated or not with EGF +/– cetuximab overnight. Final concentrations: 50 ng/mL EGF, 100 µg/mL cetuximab, and 0.5 µM lys-plasminogen.
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Figure S3. Epidermal growth factor (EGF) treatment increases percentage of thrombomodulin (TM)-positive CASKI cells in serum-free conditions. A, Representative histograms of the flow cytometry for TM of CASKI cells treated with epidermal growth factor (EGF) and cetuximab alone or in combination, for 6 h. B, Quantification of TM-positive events. Statistical analysis was performed using one-way ANOVA with Tukey's post-test. Final concentrations: 50 ng/mL EGF and 100 µg/mL cetuximab.