Researchers say they’ve identified 20 proteins specific to primary effusion lymphoma (PEL).
The proteins, which were found by growing PEL cells in culture and analyzing the secretome, may explain PEL pathogenesis, its peculiar cell adhesion, and migration patterns.
The investigators also uncovered related oncogenic pathways, which could pave the way for more individualized treatment of PEL.
These findings appear in The American Journal of Pathology.
The researchers analyzed secretomes from 4 established PEL cell lines—CRO-AP2, CRO-AP3, CRO-AP5, and CRO-AP6—as well as from 4 PEL clinical samples and 3 primary solid lymphomas. PEL cells are characterized by Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, and the primary solid lymphomas were KSHV-positive as well.
The investigators measured protein content using 2 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 the 266 proteins identified, 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 study author Annunziata Gloghini, PhD, of Istituto Nazionale dei Tumori in Milan, Italy.
“Importantly, 27 proteins were shared by secretomes from all PEL cell lines.”
The PEL secretomes were enriched with proteins specifically involved in inflammation and the immune response—such as HMGB1, GRAA, and PCBP2—as well as cell growth—such as LEG1, STMN1, and S10A6.
Other proteins are known to play roles in mRNA processing—such as ANM1 and PCBP2—or cell structure, adhesion, migration, and organization—such as EZRI and MOES. Some of the proteins have enzymatic activity—such as CATA and GSTK1.
A comparison of secretomes from PEL with those from other tumor cell lines revealed 20 proteins specific to the PEL cell lines. This suggests secretome profiling provides a source of tumor biomarkers and may ultimately improve patient management, the researchers said.
The group also conducted pathway/network enrichment analyses and found that the pathways most activated in PEL cell lines were involved with the regulation of autophagy through LRRK2-mediated signaling pathways and with apoptosis and survival through granzyme A signaling.
“The extracellular functions of granzyme A might be involved in the particular tropism of PEL and its cell growth,” said study author Italia Bongarzone, PhD, also of the Istituto Nazionale dei Tumori.
“Further studies are needed to confirm and validate the importance of these pathways/processes and their roles in lymphoma tumorigenesis and progression.”
