Rabbit Anti-Human RXFP3 (C-terminal) Polyclonal antibody

Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as elevated expression of the respective receptors and the relaxin receptor RXFP1 in the tumour tissue. It is also associated with enhanced infiltration by tumour-associated macrophages which are known to promote tumour progression. Additionally, we show in an ex vivo model of metastatic brain colonization that porcine relaxin as well as human brain-specific relaxin-3 promotes invasion into the brain tissue and enhance interaction of breast cancer cells with the resident brain macrophages, the microglia. Relaxin signaling is mediated via RXFP1, since R 3/I5, a specific agonist of the relaxin-3 receptor RXFP3 in the brain, does not significantly enhance invasion. Taken together, these findings strongly support a role of relaxins in the progression of breast cancer where they foster primary tumour growth as well as metastatic colonization by direct and indirect means.

The relaxin-like peptides produce their effects by acting at four G-protein-coupled receptors (GPCRs) RXFP1 to 4. RXFP1 and 2 are characterized by large extracellular domains containing leucine-rich repeats, whereas RXFP3 and 4 closely resemble small-peptide-liganded GPCRs. Studies with mutant RXFP1 receptors established that the final 10 amino acids of the C-terminus and Arg(752) in particular are obligatory for the second phase of cAMP signaling. Examination of the importance of cell type revealed different patterns of cAMP signaling related to the types of G-proteins expressed in these cells. Studies of RXFP3 signaling using reporter genes revealed that both relaxin and relaxin-3 activated the receptor but displayed different patterns of signaling. The studies suggest that the functional domains of the receptor, the cell type in which it is expressed, and the ligand used to activate the receptor all have important roles in determining the functional response observed.