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Compressed Prostate Cancer Cells Decrease Osteoclast Activity While Enhancing Osteoblast Activity In Vitro.

Victor J B van Santen1, Behrouz Zandieh Doulabi1, Cornelis M Semeins1

  • 1Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 LA Amsterdam, The Netherlands.

International Journal of Molecular Sciences
|January 8, 2023
PubMed
Summary
This summary is machine-generated.

Mechanical compression of prostate cancer cells alters gene expression and paracrine signaling. This impacts bone cell activity, reducing osteoclast resorption and potentially increasing osteoblast bone formation, offering insights into bone metastasis therapies.

Keywords:
adipose tissue-derived mesenchymal stromal cellbone metastasisbone remodelingepithelial-to-mesenchymal transitionpressure

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Area of Science:

  • Biomedical Engineering
  • Cancer Biology
  • Cellular Mechanobiology

Background:

  • Prostate cancer bone metastasis involves cancer cells experiencing mechanical compression (~2 kPa).
  • Mechanical stimuli can influence cancer cell behavior and signaling.

Purpose of the Study:

  • To investigate the effect of 2 kPa compression on prostate cancer cell epithelial-to-mesenchymal transition (EMT).
  • To determine how compression alters paracrine signals affecting osteoclast and osteoblast activity.

Main Methods:

  • Human DU145 prostate cancer cells were subjected to 2 kPa compression.
  • Gene expression changes were quantified using qPCR.
  • Conditioned media from compressed cells were used to treat human monocytes (osteoclasts) and adipose stromal cells (osteoblasts).

Main Results:

  • Compression altered EMT-related gene expression in DU145 cells.
  • Conditioned media from compressed cells decreased osteoclast resorptive activity by 38%.
  • Conditioned media increased osteoblast bone nodule production in a donor-dependent manner.

Conclusions:

  • Mechanical compression influences prostate cancer cell EMT and paracrine signaling.
  • Altered signaling affects bone cells, decreasing osteoclast resorption and increasing osteoblast mineralization.
  • Findings provide insights into the mechanical regulation of bone metastases and potential therapeutic targets.