The human secretome atlas initiative: Implications in health and disease conditions

Abstract

Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts towards secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study.

Glandular Proteome Identifies Antiprotease Cystatin C as a Critical Modulator of Airway Hydration and Clearance

“…This finding is similar to those of a recent study evaluating the ASL proteome of CF and non-CF HBE cultures, which demonstrated that the majority of differentially expressed proteins was elevated in CF (26). An unexpected finding was the inclusion of many intracellular proteins and membrane-associated proteins ( Figure 1D), with only 25.6% (z668 protein) of the total 2,608 proteins being classified as known secreted proteins (27) (Figure 1E, Table E2B). …”

Deconvoluting the Obesity and Breast Cancer Link: Secretome, Soil and Seed Interactions

“…Endocrine signaling between distant organ systems and tumor cells, as well as paracrine signaling between tumor and host cells in the local microenvironment, is mediated by an increasingly large roster of obesity-responsive hormones, growth factors, nutrient metabolites, chemokines and cytokines that promote tumor development and/or progression. To date, these factors (summarized below) have been studied primarily by low-throughput methods such as singleplexed or multiplexed immunoassays of serum, plasma or other biologic fluids, but high-throughput proteomic and metabolomic approaches to characterize the secretomes of organisms or cancer cells are being developed to more broadly identify the key factors (and their interactions) underlying disease states such as breast cancer [18]. …”

Antioxidant peroxiredoxin 6 protein rescues toxicity due to oxidative stress and cellular hypoxia in vitro, and attenuates prion-related pathology in vivo

“…Astrocytes are the predominant source of brain Prdx6 (Asuni et al, 2014; Lafon-Cazal et al, 2003; Yang et al, 2005), and its expression has been documented in several cell compartments, including the cytoplasm, secretory organelles, lysosomes and mitochondria (Eismann et al, 2009; Immenschuh and Baumgart-Vogt, 2005; Peshenko et al, 1998; Wu et al, 2006). It is also present in CSF, plasma and urine (Brown et al, 2013). …”