lactoferrin and Lymphoma--Large-B-Cell--Diffuse

Central nervous system (CNS) relapse is a devastating complication that occurs in about 5% of diffuse large B-cell lymphoma (DLBCL) patients. Currently, there are no predictive biological markers. We wanted to study potential biomarkers of CNS tropism that play a role in adhesion, migration and/or in the regulation of inflammatory responses. The expression levels of ITGA10, CD44, PTEN, cadherin-11, CDH12, N-cadherin, P-cadherin, lactoferrin and E-cadherin were studied with IHC and IEM. GEP was performed to see whether found expressional changes are regulated at DNA/RNA level. IHC included 96 samples of primary CNS lymphoma (PCNSL), secondary CNS lymphoma (sCNSL) and systemic DLBCL (sDLBCL). IEM included two PCNSL, one sCNSL, one sDLBCL and one reactive lymph node samples. GEP was performed on two DLBCL samples, one with and one without CNS relapse. CNS disease was associated with enhanced expression of cytoplasmic and membranous ITGA10 and nuclear PTEN (P < 0.0005, P = 0.002, P = 0.024, respectively). sCNSL presented decreased membranous CD44 and nuclear and cytoplasmic cadherin-11 expressions (P = 0.001, P = 0.006, P = 0.048, respectively). In PCNSL lactoferrin expression was upregulated (P < 0.0005). IEM results were mainly supportive of the IHC results. In GEP CD44, cadherin-11, lactoferrin and E-cadherin were under-expressed in CNS disease. Our results are in line with previous studies, where gene expressions in extracellular matrix and adhesion-related pathways are altered in CNS lymphoma. This study gives new information on the DLBCL CNS tropism. If further verified, these markers might become useful in predicting CNS relapses.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cadherins; Central Nervous System; Central Nervous System Diseases; Female; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Integrin alpha Chains; Lactoferrin; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; PTEN Phosphohydrolase

The human neutrophil lactoferrin (Lf), a cationic iron-binding glycoprotein, has an inhibitor role on granulocyte macrophage colony-stimulating factor (GM-CSF) production via interleukin-1 (IL-1). The nuclear localization of Lf suggests that it may be involved in the transcriptional regulation of GM-CSF gene expression. To explore this possibility, the effect of Lf on GM-CSF gene expression was investigated in various cell lines and in primary cultures of fibroblasts. Down-regulation of GM-CSF mRNA level was observed in Lf-transfected embryonic fibroblasts induced to produce GM-CSF by IL-1 beta. In 5637 cell-line and in embryonic fibroblasts, co-transfection experiments, in which an Lf expression vector was used together with a vector carrying a reporter gene linked to the GM-CSF promoter, revealed that Lf reduces the activity of the GM-CSF promoter. This effect is marked in IL-1 beta-stimulated cells. These findings suggest that Lf plays a negative role in GM-CSF expression at the transcriptional level, perhaps through the mediation of IL-1 beta.

Topics: Carcinoma; Cells, Cultured; Depression, Chemical; Fibroblasts; Gene Expression Regulation; Genes, Reporter; Genetic Vectors; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-1; Lactoferrin; Lung; Lymphoma, Large B-Cell, Diffuse; Promoter Regions, Genetic; Recombinant Fusion Proteins; RNA, Messenger; T-Lymphocytes; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Topics: Adenocarcinoma; Animals; Breast Feeding; Colonic Neoplasms; Depression, Chemical; Diarrhea, Infantile; Endotoxins; Female; Humans; Immunity, Maternally-Acquired; Immunoglobulin A, Secretory; Infant, Newborn; Interleukin-6; Lactoferrin; Lipopolysaccharides; Lymphoma, Large B-Cell, Diffuse; Mice; Mice, Inbred C3H; Milk, Human; Pregnancy; Spleen; Tumor Cells, Cultured; Weight Loss