Extended Data Fig. 3: Supermeres increase lactate release and transfer drug resistance.

a, Lactate release from CC cells treated with PBS (CTL), or 5 or 50 µg/ml of the sEV-P or exomeres derived from CC, SC or CC-CR cells is plotted. Data are mean ± s.e.m. n = 3 biological replicates. b, GSEA analysis of pathways enriched in metabolic enzymes for supermeres versus sEVs (top) and supermeres versus exomeres (bottom) from DiFi cells c, CC colony growth analysis in 3D collagen treated with 50 µg/ml of CC or CC-CR-derived sEV-P or exomeres in the presence or absence of cetuximab (CTX) for 14 days. Colony counts are plotted (mean ± s.e.m). n = 3 biological replicates. d, CC colony growth analysis in 3D collagen treated with 5 or 50 µg/ml of the sEV-P or exomeres derived from CC, SC, or CC-CR cells in the presence or absence of CTX for 14 days. Colony counts are plotted (mean ± s.e.m). n = 3 biological replicates. e, DiFi colony growth analysis in 3D collagen treated with 25 µg/ml of supermeres derived from SC cells in the presence or absence of CTX for 14 days. Colony counts are plotted (mean ± s.e.m). n = 3 biological replicates. f, Representative images of DiFi colonies from (e). Scale bar, 200 µm. g, CC colony growth analysis in 3D collagen treated with 25 µg/ml of supermeres derived from DiFi cells in the presence or absence of CTX for 14 days. Colony counts are plotted (mean ± s.e.m). n = 3 biological replicates. *P < 0.01 (two-tailed t-test). h, Representative images of DiFi colonies from (Fig. 3j). Scale bar, 200 µm.