Relaxin-like peptides are novel regulators of S100A4 (metastasin) expression in human thyroid carcinoma cells

Abstract

The peptide growth factor relaxin is present in human thyroid carcinoma cells but not in normal thyroid cells. We have shown that relaxin increases cellular motility and migration in human thyroid carcinoma cells via a LGR7 relaxin receptor-dependent pathway. The small calcium-binding protein S100A4 (metastasin, mts1, p9Ka, FSP1) is known as a marker for poor prognosis in human carcinomas of the breast and thyroid. The expression of S100A4 is associated with invasiveness and metastasis in different human thyroid carcinomas. We have investigated various carcinoma cell lines derived from follicular, papillary and undifferentiated thyroid primary carcinomas or their metastases and detected S100A4 mRNA in all of these human cell lines. Stable transfectants of the human follicular thyroid carcinoma cell line FTC-133 over-expressing either relaxin or the related peptide INSL3 revealed higher transcript and protein levels of S100A4 when compared to the vector-control transfectants. Untransfected FTC-133 cells exposed to human recombinant relaxin or INSL3 also responded with an increase in S100A4 transcript and protein levels identifying both RLN and INSL3 as novel inducers of S100A4.