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

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.