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!
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
Chlamydia: How bacteria take over control
28.03.2017 | Julius-Maximilians-Universität Würzburg
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Physics and Astronomy
28.03.2017 | Health and Medicine
28.03.2017 | Life Sciences