A mechanobiological model of bone metastasis reveals that mechanical stimulation inhibits the pro-osteolytic effects of breast cancer cells

Vatsal Kumar; Syeda M Naqvi; Anneke Verbruggen; Eoin McEvoy; Laoise M McNamara

doi:10.1016/j.celrep.2024.114043

A mechanobiological model of bone metastasis reveals that mechanical stimulation inhibits the pro-osteolytic effects of breast cancer cells

Cell Rep. 2024 Apr 18;43(5):114043. doi: 10.1016/j.celrep.2024.114043. Online ahead of print.

Authors

Vatsal Kumar¹, Syeda M Naqvi¹, Anneke Verbruggen¹, Eoin McEvoy², Laoise M McNamara³

Affiliations

¹ Mechanobiology and Medical Device Research Group (MMDRG), Biomedical Engineering, College of Science and Engineering, University of Galway, H91 HX31 Galway, Ireland.
² Biomedical Engineering, College of Science and Engineering, University of Galway, H91 HX31 Galway, Ireland.
³ Mechanobiology and Medical Device Research Group (MMDRG), Biomedical Engineering, College of Science and Engineering, University of Galway, H91 HX31 Galway, Ireland. Electronic address: laoise.mcnamara@universityofgalway.ie.

PMID: 38642336
DOI: 10.1016/j.celrep.2024.114043

Abstract

Bone is highly susceptible to cancer metastasis, and both tumor and bone cells enable tumor invasion through a "vicious cycle" of biochemical signaling. Tumor metastasis into bone also alters biophysical cues to both tumor and bone cells, which are highly sensitive to their mechanical environment. However, the mechanobiological feedback between these cells that perpetuate this cycle has not been studied. Here, we develop highly advanced in vitro and computational models to provide an advanced understanding of how tumor growth is regulated by the synergistic influence of tumor-bone cell signaling and mechanobiological cues. In particular, we develop a multicellular healthy and metastatic bone model that can account for physiological mechanical signals within a custom bioreactor. These models successfully recapitulated mineralization, mechanobiological responses, osteolysis, and metastatic activity. Ultimately, we demonstrate that mechanical stimulus provided protective effects against tumor-induced osteolysis, confirming the importance of mechanobiological factors in bone metastasis development.

Keywords: CP: Cancer; bone metastasis; computational models; in vitro models; mechanobiology; multicellular models; osteoblasts; osteoclastogenesis; osteolysis; tumor growth; vicious cycle.