Secreted proteins as a fundamental source for biomarker discovery

Abstract

The proteins secreted by various cells (the secretomes) are a potential rich source of biomarkers since they reflect various states of the cells at real time and at given conditions. To have accessible, sufficient and reliable protein markers is desirable since they mark various stages of disease development and their presence/absence can be used for diagnosis, prognosis, risk stratification and therapeutic monitoring. As direct analysis of blood/plasma, a common and noninvasive patient screening method, can be difficult for candidate protein biomarker identification, the alternative/complementary approaches are required, one of them is the analysis of secretomes in cell conditioned media in vitro. Since the proteins secreted by cells as a response to various stimuli are most likely secreted into blood/plasma, the identification and preselection of candidate protein biomarkers from cell secretomes with subsequent validation of their presence at higher levels in serum/plasma is a promising approach. In this review, we discuss the proteins secreted by three progenitor cell types (smooth muscle, endothelial and cardiac progenitor cells) and two adult cell types (neonatal rat ventrical myocytes and smooth muscle cells) which can be relevant to cardiovascular research and which have been recently published in the literature. We found, at least for secretome studies included in this review, that secretomes of progenitor and adult cells overlap by 48% but the secretomes are very distinct among progenitor cell themselves as well as between adult cells. In addition, we compared secreted proteins to protein identifications listed in the Human Plasma PeptideAtlas and in two reports with cardiovascular-related proteins and we performed the extensive literature search to find if any of these secreted proteins were identified in a biomarker study. As expected, many proteins have been identified as biomarkers in cancer but 18 proteins (out of 62) have been tested as biomarkers in cardiovascular diseases as well.

Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Exosomal Proteins Following Epithelial-Mesenchymal Transition

“…Crosstalk is possible, either physically or via secretion of components such as extracellular matrix (ECM) proteins, enzymes, or paracrine signaling molecules such as growth factors and inflammatory cytokines (collectively referred to as the secretome) (17)(18)(19). Given that cancer cells at the leading tumor edge can undergo EMT and initiate metastatic lesion formation in response to signals from the microenvironment (11,20), considerable effort has been directed toward characterizing the tumor secretome (21,22). To identify extracellular modulators of EMT, which may influence tumor cell state and invasive potential, we have previously analyzed the secretome (soluble-secreted proteins) from Madin-Darby canine kidney (MDCK) and Ras-transformed MDCK (21D1) cells (23,24).…”

Novel bioinformatic identification of differentially expressed tissue-specific and cancer-related proteins from the Human Protein Atlas for biomarker discovery

“…Secreted proteins can serve as biomarkers for early cancer detection and diagnosis, and membrane proteins may be potentially effective therapeutic targets (Arcinas et al, 2009;Stastna and Van Eyk, 2012). Due to the fact that the highly abundant proteins comprise 99% of the total protein mass in the blood (Loo et al, 2010), the discovery of poorly expressed cancer-specific proteins in the blood by routine biotechnology becomes difficult.…”

Detection of tumor-associated antigens in culture supernatants using autoantibodiesin sera from patients with bladder cancer

“…Thus, proteins secreted into several body fluids, such as the serum, urine, cerebrospinal fluid, tears, and saliva from tumor cells and conditioned media of cultured tumor cells have been investigated. Approximately 20-25% of cellular proteins are secreted into extracellular spaces, and these proteins play important roles in differentiation, invasion, metastasis, angiogenesis, and the regulation of cell-to-cell and cellto-extracellular matrix interactions (6,40,48). It has been suggested that tumor-secreting proteins are a promising source of diagnostic biomarkers in tumors (33).…”