Acidic extracellular pH of tumors induces octamer-binding transcription factor 4 expression in murine fibroblasts in vitro and in vivo.

Avik Som,Sharon Bloch,Samuel Achilefu,Joseph E. Ippolito

doi:10.1038/srep27803

Abstract

Octamer-binding transcription factor 4 (OCT-4) is an important marker of cellular de-differentiation that can be induced by environmental stressors, such as acidity. Here we demonstrate that chronic acidic stress in solid tumors induced OCT-4 expression in fibroblasts and other stromal cells in four tumor models. The results have implications for how tumors utilize pH modulation to recruit associated stromal cells, induce partial reprogramming of tumor-associated stromal cells, and respond to therapy.

Highlights

The extracellular pH of tumors has been implicated in the metastasis and behavior of tumor cells, and changes in this pH could modify the downstream behavior of cancer[18]
This is the first report of the expression of OCT-4 in the vicinity of tumors, in supporting stromal cells
Our data suggests that chronic mild acidity, which is present in the tumor environment along with other stressors, is capable of inducing OCT-4 expression in murine fibroblasts and may be sufficient to induce OCT-4 expression in vivo

Summary

Introduction

Absence of cancer cells, OCT-4 expression in the 3T3 cells did not increase over time (Fig. 1a). Co-culture of these fibroblasts with tumor cells at pH 7.4 resulted in increased OCT-4 expression (Fig. 1b,c). The enhanced nuclear localization of OCT-4 indicates that tumor cells can facilitate OCT-4 expression in surrounding healthy tissue under normal physiological pH.

Results

Conclusion