The Relaxin peptide is a novel regulator of S100A4 (metastasin) in thyroid carcinoma cells
Yvonne Radestock1, Cuong Hoang-Vu1 & Sabine Hombach-Klonisch2
The peptide growth factor relaxin (RLN) is expressed in human thyroid carcinoma cell lines and tissues. We have previously established thyroid carcinoma cell transfectants with over-expression of relaxin and demonstrated that relaxin increases cellular motility and in-vitro invasiveness in these transfectants. This increase in motility and migration is relaxin receptor (LGR7)-dependent. S100A4 (metastasin), a member of the S100 family of calcium binding proteins, is known to confer invasiveness in breast cancer cells and its expression in carcinoma tissues correlated with advanced stages of the disease. S100A4 is considered a molecular marker for the metastatic potential for carcinoma with high prognostic significance. We have shown that S100A4 is increased in thyroid adenoma, in papillary, follicular and anaplastic thyroid carcinoma tissues as compared to goiter tissues and S100A4 protein is localized in the cytoplasm of tumor cells. Highest intra-tumor levels of S100A4 expression were detected in papillary thyroid carcinoma with nodal metastasis. We show here that the relaxin/LGR7 ligand-receptor system is a novel transcriptional regulator of S100A4 expression in thyroid carcinoma cell line FTC133. The relaxin-mediated increase in motility is mediated by an increased expression of S100A4 mRNA and protein. Furthermore, S100A4 siRNA knock-down prevented the relaxin-induced increase in cellular motility of the cell line FTC-133. Thus, relaxin expression is a novel regulator of S100A4 in thyroid carcinoma cells and S100A4 may mediate the relaxin-induced increase in cancer cell invasiveness.