Overexpression of SMARCE1 is associated with CD8+ T-cell infiltration in early stage ovarian cancer

Antonis Giannakakis; Athanasios Karapetsas; Denarda Dangaj; Evripidis Lanitis; Janos Tanyi; George Coukos; Raphael Sandaltzopoulos

doi:10.1016/j.biocel.2014.05.031

Overexpression of SMARCE1 is associated with CD8+ T-cell infiltration in early stage ovarian cancer

Int J Biochem Cell Biol. 2014 Aug:53:389-98. doi: 10.1016/j.biocel.2014.05.031. Epub 2014 May 29.

Authors

Antonis Giannakakis¹, Athanasios Karapetsas², Denarda Dangaj³, Evripidis Lanitis³, Janos Tanyi⁴, George Coukos⁵, Raphael Sandaltzopoulos⁶

Affiliations

¹ Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece; Division of Genome and Gene Expression Data Analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), Singapore 138671, Singapore.
² Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece.
³ Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece; Department of Oncology, Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
⁴ Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia, USA.
⁵ Department of Oncology, University Hospital of Lausanne (CHUV), Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
⁶ Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address: [email protected].

PMID: 24880093
DOI: 10.1016/j.biocel.2014.05.031

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: CD8+ T-cell infiltration; CXCL9; Early ovarian cancer; SMARCE1; Termination transcription factor 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / pathology*
Cell Line, Tumor
Chemokine CXCL9 / biosynthesis
Chromosomal Proteins, Non-Histone / biosynthesis*
DNA-Binding Proteins / biosynthesis*
Female
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Staging*
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / pathology
Transcription Factors

Substances

CXCL9 protein, human
Chemokine CXCL9
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
SMARCE1 protein, human
TTF1 protein, human
Transcription Factors