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Bone-homing Metastatic Breast Cancer Cells Impair Osteocytes' Mechanoresponse in a 3D Loading Model

Overview
Journal Heliyon
Specialty Social Sciences
Date 2023 Sep 28
PMID 37767467
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Abstract

Breast cancer predominantly metastasizes to the skeleton. Mechanical loading is reliably anabolic in bone, and also inhibits bone metastatic tumor formation and bone loss in vivo. To study the underlying mechanisms, we developed a 3D culture model for osteocytes, the primary bone mechanosensor. We verified that MLO-Y4s responded to perfusion by reducing their and gene expression. We next cultured MLO-Y4s with tumor-conditioned media (TCM) collected from human breast cancer cells (MDA-MB-231s) and a corresponding bone-homing subclone to test the impacts on osteocytes' mechanosensation. We found that TCM from the bone-homing subclone was more detrimental to MLO-Y4 growth and viability, and it abrogated loading-induced changes to . Our studies demonstrate that MLO-Y4s, including their mechanoresponse to perfusion, were more negatively impacted by soluble factors from bone-homing breast cancer cells compared to those from parental cells.

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Verbruggen S J Bone Oncol. 2024; 44:100526.

PMID: 38304485 PMC: 10831278. DOI: 10.1016/j.jbo.2024.100526.

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