Fig. 1. Netrin-1 blockade inhibits endometrial adenocarcinoma progression in preclinical models.
a, Diagram showing the experimental strategy used to induce Pten deletion into CAG-CreERT2+/−Pten f/f mice using tamoxifen injection and either treatment with NP137 or control. Mice were euthanized if they experienced breathing difficulties15. b, Relative messenger RNA expression of netrin-1 as defined by RT–qPCR in the endometrium of CreERT2–/– animals (n = 12) and in tumours induced following Pten deletion (tamoxifen injection) in CreERT2+/− Pten f/f mice intraperitoneally treated with NP137 (10 mg kg–1) (n = 12) and in control (n = 5). Bars are mean ± s.e.m.; data normalized to HPRT gene; Cp, crossing point. ***P < 0.001 CreERT2+/– versus CreERT2–/– and #P = 0.0284 NP137 versus control by Mann–Whitney two-sided test. c, Representative netrin-1 IHC analysis of EC in CreERT2+/− Pten f/f mouse following 6 weeks of tamoxifen injection. Scale bar, 100 µm. d, Kaplan–Meier curves indicating percentage survival for normal mice (CreERT2–/–, red, n = 8), Pten-deleted mice treated with NP137 (green, n = 14) and control (blue, n = 11). **P < 0.01 by Mantel–Cox test. e, Quantification by pathologists of endometrial lesions, presented by tumour complexity (progressively darker colour from hyperplasia through mild, then moderate, endometrial intraepithelial neoplasia to adenocarcinoma) between control mice (n = 12) and those treated with NP137 mAb (n = 16). ***P < 0.001 by chi-squared test and Fisher’s two-sided exact test. f, Representative images of H&E staining of uterus from mice killed at week 6 of tamoxifen injection, those treated with NP137 and control. Scale bar, 50 µm.