The homeodomain transcription factor MEIS1 triggers chemokine expression and is involved in CD8+ T‐lymphocyte infiltration in early stage ovarian cancer

CD8+ T‐lymphocytes infiltration is a favorable prognostic marker in ovarian cancer. Recently we identified MEIS1 as a gene overexpressed in early stage ovarian tumors enriched for CD8+ T‐cells. Here, we report the molecular mechanism of the homeodomain transcription factor MEIS1 in lymphocyte recrui...

Full description

Saved in:
Bibliographic Details
Published in:Molecular carcinogenesis 2018-09, Vol.57 (9), p.1251-1263
Main Authors: Karapetsas, Athanasios, Tokamani, Maria, Evangelou, Christos, Sandaltzopoulos, Raphael
Format: Article
Language:English
Subjects:
Carbon tetrachloride
CCL18 protein
CCL4 protein
CD8 antigen
CD8-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - pathology
Cell culture
Cell Line, Tumor
chemokine antibody arrays
Chemokines
Chemokines - genetics
chemotaxis
Chemotaxis, Leukocyte
chromatin immunoprecipitation
electrophoretic mobility shift assay
Female
Gene Expression Regulation, Neoplastic
Homeobox
Humans
Interleukin 8
Lymphocytes
Lymphocytes T
MEIS1
Metastases
Myeloid Ecotropic Viral Integration Site 1 Protein - genetics
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
siRNA
Survival analysis
Transcription factors
Tumors
Up-Regulation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:CD8+ T‐lymphocytes infiltration is a favorable prognostic marker in ovarian cancer. Recently we identified MEIS1 as a gene overexpressed in early stage ovarian tumors enriched for CD8+ T‐cells. Here, we report the molecular mechanism of the homeodomain transcription factor MEIS1 in lymphocyte recruitment. We validated that MEIS1 expression is a positive predictor of CD8+ T cells in early stage ovarian cancer. We showed that MEIS1 induces the expression of CCL18, CCL4, CXCL7, CCL5, CXCL1, and IL8 chemokines in cancer cells followed by their secretion in the culture medium ultimately triggering CD8+ T‐lymphocyte recruitment in vitro. Knock down of MEIS1 expression by siRNA resulted in downregulation of these chemokines. We verified that MEIS1 binds to the promoters of chemokine genes, both in vitro and in vivo. We also showed that the expression levels of MEIS1 correlated tightly with the mRNA levels of chemokines CCL4 and CCL18 in early stage ovarian cancer patient samples and served as a positive prognostic marker, as shown by Kaplan‐Meyer survival analysis. In conclusion, we propose that MEIS1 plays a pivotal role in the regulatory circuitry governing T‐cell chemo‐attraction during the early stages of ovarian cancer.
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.22840