Relaxin-like ligand-receptor systems are autocrine/paracrine effectors in tumor cells and modulate cancer progression and tissue invasiveness.
Relaxin and INSL3 are novel autocrine/paracrine insulin-like hormones in tumor biology. Both effectors can bind to and activate the leucine-rich G-protein coupled receptors LGR7 relaxin receptor) or LGR8 (relaxin/INSL3 receptor). These relaxin-like ligand-receptor systems modulate cellular functions and activate signaling cascades in a tumor-specific context leading to changes in tumor cell proliferation, altered motility/migration and enhanced production/secretion ofpotent proteolytic enzymes. Matrix-metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP) and acid hydrolases such as cathepsins can facilitate tissue degradation and represent important proteolytic mediators of relaxin-like actions on tumor cell invasion and metastasis. This review presents recent new findings and emphasises the important functions of the relaxin/INSL3 ligand-receptor system as novel autocrine/paracrine effectors influencing tumor progression and tissue invasiveness.
Klonisch
Thomas
T
Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, 130 Basic Medical Science Bldg., 730 William Avenue, Winnipeg, Manitoba, Canada R3E 0W3. klonisch@cc.umanitoba.ca
Bialek
Joanna
J
Radestock
Yvonne
Y
Hoang-Vu
Cuong
C
Hombach-Klonisch
Sabine
S
D000818:Animals; D019898:Autocrine Communication; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D011506:Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D007328:Insulin; C084797:Leydig insulin-like protein; D008024:Ligands; D009363:Neoplasm Proteins; D011506:Proteins; C472867:RXFP2 protein, human; D043562:Receptors, G-Protein-Coupled