Relaxin enhances the oncogenic potential of human thyroid carcinoma cells.
The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility. The increased elastinolytic activity correlated with enhanced production and secretion of the lysosomal proteinases cathepsin-D (cath-D) and cath-L forms hereby identified as new RLN2 target molecules in human neoplastic thyrocytes. We found the intracellular distribution of procath-L specifically altered in RLN2 transfectants, providing first evidence for selective actions of relaxin on the powerful elastinolytic cath-L production, storage, and secretion in thyroid carcinoma cells. Thus, relaxin enhances the oncogenic potential and acts as novel endocrine modulator of invasiveness in human thyroid carcinoma cells.
Hombach-Klonisch
Sabine
S
Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, 130 Basic Medical Sciences, 730 William Ave., Winnipeg, MB, R3E 0W3, Canada. klonisch@cc.umanitoba.ca
Bialek
Joanna
J
Trojanowicz
Bogusz
B
Weber
Ekkehard
E
Holzhausen
Hans-Jürgen
HJ
Silvertown
Josh D
JD
Summerlee
Alastair J
AJ
Dralle
Henning
H
Hoang-Vu
Cuong
C
Klonisch
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000473:pathology*; D002403:Cathepsins / Q000096:biosynthesis / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002648:Child; D004549:Elastin / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide; D012065:Relaxin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; C095068:RLN2 protein, human; D012333:RNA, Messenger; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin; D004549:Elastin; D002403:Cathepsins