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.
Department of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, USA.|Department of Biomedical Engineering, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, USA.
Avik
A
Som
Department of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, USA.
Sharon
S
Bloch
Department of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, USA.|Department of Genetics, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, USA.
Joseph E
JE
Ippolito
Department of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, USA.|Department of Biomedical Engineering, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, USA.|Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, USA.
Samuel
S
Achilefu
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D049452:Green Fluorescent Proteins