Most patients diagnosed with non-small cell lung cancer (NSCLC) have already developed distant metastases so that patient overall survival is poor. Within the metastatic process migration is one of the critical steps. Several members of Ca²⁺-activated K⁺ channels, and in particular K_Ca3.1, have been shown to be involved in cell migration or cancer progression.

Inhibition of this channel might therefore be a potential treatment option for cancer patients.

In this study, we compared two strains of the lung carcinoma cell line A549 with low and high metastatic potential in relation to the Ca²⁺-activated potassium channel K_Ca3.1. Microarray expression data from a class comparison analysis revealed significantly increased expression of this potassium channel in the highly metastatic A549 cell line. This result could be validated on the protein or mRNA level as well as with immunoflurescence.

Migration and proliferation of both cell lines were inhibited with the specific K_Ca3.1-inhibitor Tram-34. Interestingly, this inhibitory effect was stronger in the highly metastatic cell line. An opposite effect could be observed when using the K_Ca3.1 channel activator 1-ethyl-2-benzimidazolinone (1-EBIO). Only the A549 cells with high metastatic potential showed increased migration in the presence of 1-EBIO. Finally, analysis of a published microarray database of 104 samples from lung adenocarcinoma patients (Shedden, Nat Med 14: 822ff, 2008) revealed significantly poorer survival for those patients with high K_Ca3.1 expression. In conclusion, these results provide evidence that the Ca²⁺-activated K⁺- channel K_Ca3.1 might be involved in the metastatic process of non-small cell lung cancer.