Osteoblasts are "educated" by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment

Breast Cancer Research : BCR
Alexus D KolbKaren M Bussard

Abstract

In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Bone-resorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are diverted from laying down bone matrix to producing cytokines that facilitate breast cancer cell maintenance in late-stage disease. Here, we have new evidence to suggest that there are subpopulations of osteoblasts in the tumor niche as evidenced by their protein marker expression that have distinct roles in tumor progression in the bone. Tumor-bearing tibia of mice was interrogated by immunofluorescent staining for the presence of osteoblasts and alterations in niche protein expression. De-identified tissue from patients with b...Continue Reading

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Citations

Nov 13, 2019·Current Osteoporosis Reports·Bridie S MulhollandNigel A Morrison
Feb 26, 2020·Biomolecules·Jennifer ZarrerHanna Taipaleenmäki
Apr 2, 2020·Frontiers in Oncology·Marie-Therese HaiderHanna Taipaleenmäki
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Dec 2, 2020·Molecular Cancer Research : MCR·Lebaron C AgostiniJonathan R Brody
Oct 30, 2020·International Journal of Molecular Sciences·Jan BrábekKarel Smetana
Apr 4, 2021·International Journal of Molecular Sciences·Marie-Therese HaiderHanna Taipaleenmäki
May 13, 2021·Seminars in Cancer Biology·Andrea R Lim, Cyrus M Ghajar
Aug 17, 2021·Frontiers in Oncology·Maria Teresa ValentiOlivier Feron
May 23, 2021·Molecular Cancer Research : MCR·Alison B ShuppKaren M Bussard
Sep 22, 2021·Journal of Immunotherapy·Bora KimWonbong Lim

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Methods Mentioned

BETA
PCR
Assay
transfection
Protein Assay
fluorescence microscopy
bioluminescence imaging

Software Mentioned

GraphPad Prism
FlowJo
BDFACS Diva
Olympus cellSens
Living Image
IT
Olympus
cellSens Count and Measure Tool
cellSens
Click

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