1532P - New insights from KISS activity: a prognostic biomarker in malignant pleural mesothelioma

Abstract

The KISS1 gene (“KI”: in homage to the location of where it was discovered, Hershey, Pennsylvania, home of Hershey's Kiss, and “SS”: Suppressor Sequence) encodes for a 145 amino acid peptide, known as kisspeptin, which is cleaved to smaller peptides of 54 amino acid, known as metastatin. KISS1 was originally isolated in melanoma as a molecule with anti-metastatic effects. Associations between loss of KISS1 expression and increased tumor progression and poor prognosis were found in various solid tumors, including lung cancer, but the precise role of KISS1 expression is not well defined. The human mesothelioma H2452, H2052, H28 and MSTO cell lines were used. The mRNA and protein levels of KISS1, and its G-protein coupled receptor GPR54, were evaluated by qPCR and Western Blot analysis. In order to prove that kisspeptins regulate cell proliferation, migration, and invasion in mesothelioma cell lines via KISS/GPR54, we conducted in vitro treatments with different doses of kisspeptin (Kp-10) [from Kp-10-7 to Kp-10-12 M] through MTT, Scratch and Boyden Chamber assays. Finally, MMPs activity (MMP-2 and MMP-9) was examined by gelatin Zymography. The presence of KISS1 and GPR54 were found in all cell lines analyzed, both at mRNA and protein levels. Treatment with Kp-10, at dose from 10-12 to 10-10 M, significantly inhibited cell proliferation, migration and invasion of mesothelioma cell lines. In addition, Kp-10 treatment inhibited the production and activity of MMP-2 and MMP-9 determining consequently a marked reduction in the invasiveness of primary tumors and metastases. The results demonstrate a role of the KISS1/GPR54 system in malignant mesothelioma and may be used as a predictive marker of progression disease. However, further studies are required to investigate the effect of Kp-10 alone or in combination with molecular targeted agents.