We investigated the expression of slug in a large set of lung squamous and adenocarcinomas to determine common or dissimilar features in its expression in these two most common forms of lung cancer. To investigate slug related tumor spread we studied the expression of vimentin, claudin 1, MMP2 and MMP9 in these tumors and their relation to slug. Addition, cell invasion assays, mRNA analysis and zymographic tests were performed to study epitheliomesenchymal transition (EMT) related changes in slug blocked lung cell lines. According to the results slug expression did not significantly differ between squamous (SCC) and adenocarcinoma (AC) (P = 0.25). In SCC, slug associated with vimentin (P = 0.016). In AC, claudin 1 associated with MMP2 (P = 0.037). In SCC slug expression had a poor prognositic significance (P = 0.006) and it had independent prognostic value (P = 0.037). In AC MMP2 had a worsening impact on survival (P = 0.021) and it had independent prognostic value (P = 0.002). In cell invasion assays, slug knockdown inhibited the invasion and migration of BEAS-2B, SK-LU1 and SK-MES1 cell lines. The mRNA expression of claudin 1 was downregulated in SK-LU1 cell line. Both tumor cell lines expressed MMP2 and in SK-MES1 slug inhibited line MMP2 appeared to decrease. The results show that slug associated EMT is more pronounced in lung SCC than AC. Slug associated with vimentin in SCC and had an independent prognostic value in this tumor type. Forced slug inhibition might be one putative way of treatment of SCC of the lung.
Keywords: EMT; MMP; Slug; carcinoma; claudin 1; lung; vimentin.