The PTEN/PI3K/Akt pathway regulates stem-like cells in primary esophageal carcinoma cells.

Recent reports have shown that cancer stem cells exist in many malignancies. Side population (SP) cells are used to enrich cancer stem-like cells in many cell lines and fresh tumor specimens. In this study, we cultured primary esophageal squamous cell carcinoma (ESCC) cells from ESCC tissue specimens. SP cells from primary ESCC cells were more resistant to chemotherapeutic reagents and formed more colonies in vitro than non-SP cells. In addition, xenograft experiments revealed that SP cells were more tumorigenic in vivo. Further results indicated that the PI3K/Akt pathway is essential to SP cells through the regulation of ABCG2 transporter function. Furthermore, PTEN, rather than mTOR, was found to be involved in SP cell regulation in primary ESCC cells. These findings reveal that SP cells are enriched for cancer stem-like cells in primary ESCC cells and that the PTEN/PI3K/Akt pathway regulates this stem-like population. This study indicates that SP cells in primary culture cells from tissue specimens could be a promising model for cancer stem cell research and may help researchers develop novel therapeutic strategies or efficient drugs that target ESCC stem-like cells.