PTH1R-CaSR Cross Talk: New Treatment Options for Breast Cancer Osteolytic Bone Metastases

Table 2

Comparison of PTH1R and CaSR.

	PTH1R	CaSR
GPCR	Class B family	Class C family
Receptor size	Human PTH1R has 593 amino acids	Human CaSR has 1078 amino acids
Expression	Mostly in osteoblast and kidney, also in cartilage, normal breast epithelial cells, and some breast cancer cell lines	Parathyroid glands, kidney, bone, normal breast epithelial cells, and BrCa cells
G protein	Gαs, Gαq, Gαi, and G12/13	Gαi, Gαq, Gαs, and G12/13
Agonist	PTH and PTHrP	Type I: inorganic or organic polycations (Ca^2+ and Gd^3+), polyamines (spermine and spermidine), and aminoglycoside antibiotics (neomycin); Type II: positive allosteric modulators (calcimimetics)—cinacalcet, NPS R-467, NPS R-568, and AMG 416
Antagonist	PTH(7–34)	Negative allosteric modulators (calcilytics): NPS 2143
Application in treating BrCa bone metastases	Intermittent PTH(1–34) prevents BrCa bone metastases in mouse models	Cinacalcet is able to treat severe hypercalcemia caused by BrCa bone metastases