GPC-3C is a product of proteolytic activity of Furin-Convertase and accumulates in cell-derived small EVs. (a) Representative phase contrast images of CP-Hep exposed to CMK (0, 10, 25, 50, 100 µM) scale bar: 200 µm (4×) and 50 µm (20×). (b) Cellular Viability expressed in the percentage Trypan Blue negative cells exposed to CMK (One-way ANOVA ****, p < 0.001). (c) WB of CP-Hep cytoplasmic and sEV protein fractions immunoblotted for Furin, GPC-3C, GPC-3N, HSP90 and GAPDH. (d) GPC-3C densitometry in CP-Hep IB (e) Cytoplasmatic GPC-3N densitometry in CP-Hep (f) Quantification of Inactive Furin in sEVs. (g) Representative Co-IF of GPC-3N and Caspase 3 in untreated and treated (100 µM CMK) CP-Hep (scale bar: 200 µm (4×), 20 µm (63×). Statistical analysis in b, d, e, and f are performed with ordinary one-way ANOVA and Dunnett’s multiple comparison test, comparing the mean of each treated group with mean of control group, ***, p < 0.001 and ****, p < 0.0001, ns as non-significant are reported.