Acidic pH derived from cancer cells may induce failed reprogramming of normal differentiated cells adjacent tumor cells and turn them into cancer cells.

BACKGROUND: Eelier studies demonstrated the up-regulation of some transcriptional factors such as Oct4, Nanog, Sox2 in undifferentiated cancer cells. These transcriptional regulators are up-regulated in pluripotent cells, as well and are responsible for cell reprogramming in normal cells. It might be said that normal cells adjacent tumor site are undergone of failed cell reprogramming. PRESENTATION OF THE HYPOTHESIS: Extracellular pH of cancer cell is acidic and recent studies reveal the role of acidic environment in cell reprogramming of normal cells. This hypothesis deals with the potential role of acidic pH in malignant tumor development through normal cells adjacent cancer cells. It seems that cancer cells are more intelligent and acid release from these cells is not just a by-product but also and more important reason, is a tool to up-regulate cell reprogramming markers, induce epigenetic modification and tumor progress in normal cells adjacent cancer cells. If this is correct, then it could be expected that with alkaline targeting of tumor environment, failed cell reprogramming, aberrant epigenetic modification will decrease in normal cells adjacent cancer cells and afterward metastasis will decrease. TESTING THE HYPOTHESIS: It is proposed to investigate altered genetic and epigenetic modification (DNA methylation, histone modification) in cancer, early cancer and cells in vicinity of cancer cells at different pH range of 5.8-7.8. This study is performed to determine whether acidic pH induces reprogramming, global hypomethylation and promoter hypermethylation in cancer cells and cells in vicinity of cancer cells at different pH values. IMPLICATIONS OF THE HYPOTHESIS: This hypothesis deal with the ability of acidic pH to convert normal cells adjacent cancer cells to cancerous cells and its inductive potential on genetic and epigenetic modification of normal cells adjacent cancer cells and will further emphasize the important of extracellular acidic targeting in cancer therapy.