Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8323463 | The International Journal of Biochemistry & Cell Biology | 2014 | 10 Pages |
Abstract
T-lymphocyte infiltration in ovarian tumors has been linked to a favorable prognosis, hence, exploring the mechanism of T-cell recruitment in the tumor is warranted. We employed a differential expression analysis to identify genes over-expressed in early stage ovarian cancer samples that contained CD8 infiltrating T-lymphocytes. Among other genes, we discovered that TTF1, a regulator of ribosomal RNA gene expression, and SMARCE1, a factor associated with chromatin remodeling were overexpressed in first stage CD8+ ovarian tumors. TTF1 and SMARCE1 mRNA levels showed a strong correlation with the number of intra-tumoral CD8+ cells in ovarian tumors. Interestingly, forced overexpression of SMARCE1 in SKOV3 ovarian cancer cells resulted in secretion of IL8, MIP1b and RANTES chemokines in the supernatant and triggered chemotaxis of CD8+ lymphocytes in a cell culture assay. The potency of SMARCE1-mediated chemotaxis appeared comparable to that caused by the transfection of the CXCL9 gene, coding for a chemokine known to attract T-cells. Our analysis pinpoints TTF1 and SMARCE1 as genes potentially involved in cancer immunology. Since both TTF1 and SMARCE1 are involved in chromatin remodeling, our results imply an epigenetic regulatory mechanism for T-cell recruitment that invites deciphering.
Keywords
TTF1HRPCCl4PBMCsCcl5chemokine (C–C motif) ligand 5IL8CXCL9Interleukin 8TILregulated on activation, normal T cell expressed and secretedTumor infiltrating lymphocytesstandard error of meanEarly ovarian cancerperipheral blood mononuclear cellsNK cellsNatural killer cellsmacrophage inflammatory protein-1βSEMRANTESHorseradish peroxidaseAdder
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Authors
Antonis Giannakakis, Athanasios Karapetsas, Denarda Dangaj, Evripidis Lanitis, Janos Tanyi, George Coukos, Raphael Sandaltzopoulos,