The Ratio of RAGE Isoforms Is Affected by HMGB1 and Its Truncated Form Only in A549 but not in H1299 Lung Cancer Cell Lines

Abstract

The Receptor of Advanced Glycated End products (RAGE) could exist in two forms, a membrane bound and a soluble one. RAGE is highly expressed during embryonic development and decreases in all tissues except the lung in adult organisms. Lung RAGE mediates lung cancer, pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, etc. The lung cancers, among the most invasive of tumours, are reported to express low levels of RAGE. A specific RAGE ligand is the nuclear protein HMGB1. We examined the effect of HMGB1 and its truncated form lacking the C-tail (HMGB1ΔC) on RAGE expression in NSCLC cancer cell lines with different invasive capacity: A549 with better prognosis and H1299 with negative outcome. In A549 upon addition of ligands two important results are observed: (i) total RAGE expression is augmented 1.5 times and 1.7 times for HMGB1 and HMGB1ΔC, respectively, and (ii), a full-length membrane variant (flRAGE) is observed and in the presence of HMGB1ΔC its expression is comparable with the soluble one. In control H1299 lung cancer cells the dominant form of RAGE was the flRAGE while sRAGE represents one third of the whole amount of the receptor. HMGB1 and HMGB1ΔC do not affect the total RAGE amount and the ratio between flRAGE and sRAGE. In the case of lung cancer, the higher amount of RAGE is related to better prognoses and less metastatic ability which means that the stimulation of RAGE expression by HMGB1 and HMGB1ΔC in A549 is considered a positive tendency. In the case of the more aggressive lung cancer H1299 both ligands do not change the RAGE behaviour and in this way do not affect the invasive potential of the cancer cells.