Format

Send to

Choose Destination
Cell J. 2016 Winter;17(4):617-28. Epub 2016 Jan 17.

STAT3 is Overactivated in Gastric Cancer Stem-Like Cells.

Author information

1
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
2
Department of Stem Cells and Developmental Biology, Cell Sciences Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
3
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
4
Department of Molecular Medicine, Faculty of Advanced Medical Technologies, Gorgan University of Medical Sciences, Gorgan, Iran.

Abstract

OBJECTIVE:

Gastric cancer (GC) is widely associated with chronic inflammation. The pro inflammatory microenvironment provides conditions that disrupt stem/progenitor cell proliferation and differentiation. The signal transducer and activator of transcrip- tion-3 (STAT3) signaling pathway is involved in inflammation and also contributes to the maintenance of embryonic stem cell (ESCs) pluripotency. Here, we have investi- gated the activation status of STAT3 in GC stem-like cells (GCSLCs).

MATERIALS AND METHODS:

In this experimental research, CSLCs derived from the human GC cell line MKN-45 and patient specimens, through spheroid body formation, character- ized and then assayed for the STAT3 transcription factor expression in mRNA and protein level further to its activation.

RESULTS:

Spheroid cells showed higher potential for spheroid formation than the pa- rental cells. Furthemore, stemness genes NANOG, c-MYC and SOX-2 were over expressed in spheroids of MKN-45 and in patient samples. In MKN-45 spheroid cells, epithelial mesenchymal transition (EMT) related markers CDH2, SNAIL2, TWIST and VIMENTIN were upregulated (P<0.05), but we observed no change in expression of the E-cadherin epithelial marker. These cells exhibited more resistance to docetaxel (DTX) when compared with parental cells (P<0.05) according to the MTS assay. Al- though immunostaining and Western blotting showed expression of the STAT3 pro- tein in both spheroids and parents, the mRNA level of STAT3 in spheroids was higher than the parents. Nuclear translocation of STAT3 was accompanied by more intensive phospho-STAT3 (p-STAT3) in spheroid structures relative to the parent cells accord- ing to flow cytometry analysis (P<0.05).

CONCLUSION:

The present findings point to STAT3 over activation in GCSLCs. Com- plementary experiments are required to extend the role of STAT3 in stemness fea- tures and invasion properties of GCSCs and to consider the STAT3 pathway for CSC targeted therapy.

KEYWORDS:

Cancer Stem Cells; EMT; Gastric Cancer; STAT3; Spheroid

PMID:
26862521
PMCID:
PMC4746412

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center