Lysosomal acid hydrolases of the cathepsin family are novel targets of INSL3 in human thyroid carcinoma cells.
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.
Bialek
Joanna
J
Clinics of General, Visceral, and Vascular Surgery, Martin Luther University, Halle/Saale, Germany.
Hombach-Klonisch
Sabine
S
Fiebig
Barbara
B
Weber
Ekkehard
E
Hoang-Vu
Cuong
C
Klonisch
Thomas
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000378:metabolism*
D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D000255:Adenosine Triphosphate; D004549:Elastin; D006867:Hydrolases; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; D002402:Cathepsin D