Primary effusion lymphoma (PEL) is a rare B-cell neoplasm distinguished by its tendency to spread along the thin serous membranes that line body cavities without infiltrating or destroying nearby tissue.
By growing PEL cells in culture and analyzing the secretome (proteins secreted into cell-conditioned media), investigators have identified proteins that may explain PEL pathogenesis, its peculiar cell adhesion, and migration patterns. They also recognized related oncogenic pathways, thereby providing rationales for more individualized treatment. The results are published in The American Journal of Pathology.
A biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, a condition, or disease, and can help develop personalized therapeutic approaches for patients. Analysis of secretomes is a new strategy for discovering biomarkers involved in cancer pathogenesis based on the reasoning that these fluids will be enriched in proteins secreted by cancer cells, shed from cancer cell surfaces, or released from the interior of cells (through vesiculation, cell lysis, apoptosis, or necrosis). The content of the secretome may reflect the functional state of the cells at a specific time point.
In this study, investigators from the Istituto Nazionale dei Tumori of Milan and the Centro di Riferimento Oncologico of Aviano, Italy, analyzed secretomes from four established PEL cell lines (CRO-AP2, CRO-AP3, CRO-AP5, and CRO-AP6; established in the laboratories directed by Antonino Carbone, MD) as well as from four PEL clinical samples and three primary solid lymphomas. PEL tumor cells are characterized by Kaposi's sarcoma-associated herpesvirus (KSHV) infection, and the primary solid lymphomas were also KSHV-positive.
Protein content was measured using two complementary mass spectrometry platforms. The experiments allowed cells to grow for 16 to 18 hours and were performed under serum-free conditions to increase the ability to detect secreted proteins. Of 266 identified proteins, 139 (52%) were secreted and 127 were considered to have an intracellular origin or were secreted in an unconventional fashion. "Most of the proteins we recognized in the secretome of PEL are new with respect to previous studies utilizing conventional proteomic analysis and gene expression profiling," said Annunziata Gloghini, PhD, of the Department of Pathology of the Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
"Importantly, 27 proteins were shared by secretomes from all PEL cell lines," added Dr. Gloghini. The researchers found that the PEL secretomes were enriched with proteins specifically involved in inflammation and the immune response (eg, HMGB1, GRAA, and PCBP2) and cell growth (eg, LEG1, STMN1, and S10A6). Other proteins play roles in mRNA processing (eg, ANM1 and PCBP2) or cell structure, adhesion, migration, and organization (eg, EZRI, MOES). Some proteins have enzymatic activity (eg, CATA and GSTK1).
Comparison of secretomes from PEL with those from other tumor cell lines identified 20 proteins specific to the PEL cell lines. This suggests that secretome profiling provides a source of tumor biomarkers and may ultimately improve patient management.
The investigators also investigated the association between the proteins found in the PEL secretome and biological function. Using pathway/network enrichment analysis, they found that the pathways most activated in PEL cell lines were involved with regulation of autophagy (an intracellular catabolic mechanism) through LRRK2-mediated signaling pathways and with apoptosis and survival through granzyme A signal. "The extracellular functions of granzyme A might be involved in the particular tropism of PEL and its cell growth," says Italia Bongarzone, PhD, of the Department of Experimental Oncology and Molecular Medicine of the Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. "Further studies are needed to confirm and validate the importance of these pathways/processes and their roles in lymphoma tumorigenesis and progression."
Eileen Leahy | EurekAlert!
New Model of T Cell Activation
27.05.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Fungi – a promising source of chemical diversity
27.05.2016 | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (HKI)
A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.
The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...
Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.
The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...
In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.
In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...
Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices
Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.
When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene
In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...
24.05.2016 | Event News
20.05.2016 | Event News
19.05.2016 | Event News
30.05.2016 | Materials Sciences
30.05.2016 | Materials Sciences
30.05.2016 | Trade Fair News