Role of H2 relaxin in the human thyroid

The multifunctional peptide hormone relaxin has recently been identified as an important endocrine player in tumor biology. We found H2 relaxin to be exclusively expressed in human papillary, follicular and dedifferentiated thyroid carcinoma but not in hyperplastic or normal human thyroid tissues. To investigate the role of H2 in thyroid carcinoma cells, we have generated and characterized stable H2 secreting transfectants of the human follicular thyroid carcinoma cell lines FTC-133. Microarray analysis of the FTC-133 transfectants revealed changes in gene expression of enzymes affecting extracellular matrix (ECM) composition indicating a potential role of H2 relaxin in thyroid carcinoma invasiveness. Exposure to H2 resulted in significantly increased motility of both FTC cells and H2 transfectants demonstrating a role for H2 as an auto-/paracrine migratory factor. When compared with controls, H2 stable FTC-133 transfectants showed differential production as well as altered intracellular distribution and secretion of the lysosomal protease cathepsin L. This is the first demonstration of a novel role of H2 relaxin as a modulator of the cathepsin system. H2 relaxin appears to exert its effects on these highly potent ECM-degrading lysosomal proteases at multiple cellular levels which may attribute to increased motility and tissue invasion of thyroid carcinoma cells. Current studies aim at identification the cellular mechanisms leading to altered lysosomal distribution/secretion and the analysis of additional genes associated with ECM-degradation.

The study was supported by DFG.