Fig. 4: The Aβ-PrP^C axis can be targeted in vivo and has clinical relevance in basal prostate cancer and mesenchymal colon cancer.

A Top panels. Tumour growth, survival curves and number of metastases in mice bearing PC3 xenografts and treated with 5, 7.5 or 10 mg per kg of 6D11 antibody (Ab-5, Ab-7.5, Ab-10, respectively) versus control mice (Sham). Bottom panels. Tumour size (measured at autopsy for the sham and Aβ groups, and at day 40 for the Ab-10 and the Aβ + Ab-10 groups), survival curves and number of metastases in mice bearing PC3 xenografts and treated with recombinant Aβ, 6D11 antibody (at 10 mg per kg, Ab-10) or both Aβ and 6D11 antibody (Aβ + Ab-10) versus control mice (Sham). Data for tumour size and number of metastases are expressed as means ± s.e.m. of n = 5 values (*p < 0.05 and **p < 0.01 versus Sham, ^§p < 0.05 and ^§§p < 0.01 versus Aβ alone, Kruskal-Wallis and posthoc Wilcoxon rank-sum test with Holm’s correction for tumour size and number of metastases, log-rank test for survival curves. ns not significant). B Volcano plot showing the enrichment of CAV1, DKK1, DKK3 and PRNP transcripts in basal versus luminal benign prostate cancers from the Zhang study [26] (left panel); Enrichment of APP, BACE1, CAV1, DKK1, DKK3, PDGFC and PRNP transcripts in CD49f^Hi versus CD49f^Lo prostate tissue from the Smith study [27] (middle panel) (*p < 0.05 and ***p < 0.001 versus CD49f^Lo, two-tailed t-test); Volcano plot showing the upregulation of CAV1, DKK1, DKK3, PDGFC and PRNP transcripts after ADT in the Rajan study [32] (right panel). C Heatmaps showing the distribution of PRNP-associated genes in prostate cancer patients (E-MATB6128 data set) according to the PAM50 classification by Zhao [29] (left panel) or in colon cancer patients (GSE39582 dataset) according to the CMS classification by Guinney [31] (right panel). LumA: Luminal A. Lum B: Luminal B. NT: non tumour. See Supplementary Fig. S5 and S7 for statistics. D Kaplan-Meier overall survival (OS) (left panel) and relapse free survival (RFS) (right panel) according to high and low BACE1 gene expression was determined in colon cancer patients of the GSE39582 dataset. Hazard ratios were adjusted for TNM stage, MMR status and adjuvant chemotherapy.