Parathyroid hormone 1 receptor signaling mediates breast cancer metastasis to bone in mice

Bone metastases are a common complication of breast cancer. We have demonstrated that intermittent administration of parathyroid hormone (PTH[1-34]) reduces the incidence of bone metastases in murine models of breast cancer by acting on osteoblasts to alter the bone microenvironment. Here, we examin...

Full description

Saved in:
Bibliographic Details
Published in:JCI insight 2023-03, Vol.8 (5)
Main Authors: Swami, Srilatha, Zhu, Hui, Nisco, Aria, Kimura, Takaharu, Kim, Matthew J, Nair, Vaisakh, Wu, Joy Y
Format: Article
Language:English
Subjects:
Animals
Bone biology
Melanoma
Melanoma, Cutaneous Malignant
Mice
Oncology
Parathyroid Hormone
Parathyroid Hormone-Related Protein - genetics
Receptor, Parathyroid Hormone, Type 1 - metabolism
Skin Neoplasms
Tumor Microenvironment
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bone metastases are a common complication of breast cancer. We have demonstrated that intermittent administration of parathyroid hormone (PTH[1-34]) reduces the incidence of bone metastases in murine models of breast cancer by acting on osteoblasts to alter the bone microenvironment. Here, we examined the role of signaling mediated by PTH 1 receptor (PTH1R) in both osteoblasts and breast cancer cells in influencing bone metastases. In mice with impaired PTH1R signaling in osteoblasts, intermittent PTH did not reduce bone metastasis. Intermittent PTH also did not reduce bone metastasis when expression of PTH1R was knocked down in 4T1 murine breast cancer cells by shRNA. In 4T1 breast cancer cells, PTH decreased expression of PTH-related protein (PTHrP), implicated in the vicious cycle of bone metastases. Knockdown of PTHrP in 4T1 cells significantly reduced migration toward MC3T3-E1 osteoblasts, and migration was further inhibited by treatment with intermittent PTH. Conversely, overexpression of PTHrP in 4T1 cells increased migration toward MC3T3-E1 osteoblasts, and this was not inhibited by PTH. In conclusion, PTH1R expression is crucial in both osteoblasts and breast cancer cells for PTH to reduce bone metastases, and in breast cancer cells, this may be mediated in part by suppression of PTHrP.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.157390