Insulin-like
peptide 3 (INSL3) is present in hyperactive and neoplastic thyrocytes, but the functional role of this
relaxin-like
peptide hormone during
carcinogenesis in the thyroid gland is currently unknown. We generated new cell models of stable transfectants of the human
follicular thyroid carcinoma cell line FTC-133 expressing and secreting bioactive human INSL3. These transfectants displayed higher intracellular
ATP levels, but INSL3 failed to act as a promoter of growth. The acquisition of an invasive
tumor cell phenotype with local tissue invasion represents the beginning of a number of events leading to
metastasis, the major cause of fatal outcome in
cancer patients. Here we demonstrate a function of INSL3 in
elastin degradation, which is considered an early step during basal membrane penetration and tissue invasion by
tumor cells. INSL3 markedly increased the production of the lysosomal
enzymes cathepsin-L and
cathepsin-D. Enhanced secretion of the elastinolytic
cathepsin-L was associated with increased elastinolytic activity of FTC-133-INSL3 transfectants. Thus, we provide the first evidence that the INSL3
peptide can promote early
tumor cell invasiveness in human
thyroid carcinoma cells by enhancing their metabolic activity and
elastin-degrading potential.