Breast Cancer Degradomic View Figure 1. The proteome and degradome profiles for the 15 BCP and control HP samples. The degradome is a sub-proteome that participates in the proteolytic activities and produces peptidome (top). The proteomic and degradomic measurements are represented by tryptic peptides and peptidome peptides, respectively (middle). The BCP degradome is compared to the HP degradome using the peptidome peptide abundances (bottom). Details for each degradome substrate, peptidome peptide and its quantification, proteome protein, and tryptic peptide are given in Tables S1 and S2. doi:10.1371/journal.pone.0013133.g001 domains. MG4 and MG5 release the greatest numbers of peptides, while MG7 and helix domains release peptides only in the BCP. Convertases C4b and factor B (fB) that activate C3 to C3b in the lectin, classical, and alternative pathways are differentially degraded in the BCP (Figures 7B and 7C) with releasing ,3- fold more peptidome peptides than in HP (Table S2). The differential degradation of C4b and fB occur to C4a, C4b, fBa, and fBb domains. In addition to the complement system convertases, the complement system membrane attack complex (MAC) key components C8 and C9 are also differentially degraded in the BCP (Figures 8A and 8B). The differential degradation occurs to the a chains of C8 and C9. These peptidomic-degradomic evidences show that the BCP examined have excessive proteolysis destruction of the convertases and MAC components, which could hinder initiating and/or result in dysfunction of the immune complement system (Figure S2). Consistent with previous report that C3, C4, C8, and C9 are deposited on the breast cancer cell surface [32], the selective and differential degradation observed for the tested BCP are at the surface attachment domains of these convertases and components. The BCP degradome active substrates also encompass proteins that have been previously investigated individually for cancer therapy, although the roles of some of these proteins in tumor biology have not been well elucidated. Figures 9A–C shows PLoS ONE | www.plosone.org 3 October 2010 | Volume 5 | Issue 10 | e13133