In vitro and in vivo expression of aldehyde dehydrogenase 1 in oral squamous cell carcinoma.

Aldehyde dehydrogenase isoform 1 (ALDH1) is a useful marker of cancer-initiating cells (CICs) in various organs. In this study, we investigated whether alterations in ALDH1 immunostaining and enzymatic activity in tumor cell populations predicted clinicopathological factors of prognostic importance for cancer progression and contributed to the characteristics of CICs in cisplatin-treated oral squamous cell cancer (OSCC) cells. We evaluated the association between the proportion of ALDH1-positive tumor cells and the clinicopathological features in 90 patients with OSCC. We also examined ALDH1 enzymatic activity, ABCG2 expression, invasive capacity and the ability to self-renew in OSCC cells treated with or without cisplatin. The clinicopathological results showed that elevated ALDH1 expression correlated with local recurrence. In in vitro experiments, the percentage of cells exhibiting ALDH1 enzymatic activity significantly increased among cisplatin-surviving cells (CiSCs) according to flow cytometry. Furthermore, CiSCs demonstrated upregulated expression of ABCG2, their invasive capacity increased, and their ability to generate cancer spheres was enhanced. An increased population of cells exhibiting ALDH1 immunostaining is a predictive marker of local recurrence. ALDH1 expression and activity contributes to the characteristics of CICs in OSCC.