A microfluidic 3D invitro model for specificity of breast cancer metastasis to bone

Simone Bersini, Jessie S. Jeon, Gabriele Dubini, Chiara Arrigoni, Seok Chung, Joseph L. Charest, Matteo Moretti, Roger D. Kamm

Research output: Contribution to journalArticlepeer-review

412 Citations (Scopus)

Abstract

Cancer metastases arise following extravasation of circulating tumor cells with certain tumors exhibiting high organ specificity. Here, we developed a 3D microfluidic model to analyze the specificity of human breast cancer metastases to bone, recreating a vascularized osteo-cell conditioned microenvironment with human osteo-differentiated bone marrow-derived mesenchymal stem cells and endothelial cells. The tri-culture system allowed us to study the transendothelial migration of highly metastatic breast cancer cells and to monitor their behavior within the bone-like matrix. Extravasation, quantified 24h after cancer cell injection, was significantly higher in the osteo-cell conditioned microenvironment compared to collagen gel-only matrices (77.5±3.7% vs. 37.6±7.3%), and the migration distance was also significantly greater (50.8±6.2μm vs. 31.8±5.0μm). Extravasated cells proliferated to form micrometastases of various sizes containing 4 to more than 60 cells by day 5. We demonstrated that the breast cancer cell receptor CXCR2 and the bone-secreted chemokine CXCL5 play a major role in the extravasation process, influencing extravasation rate and traveled distance. Our study provides novel 3D invitro quantitative data on extravasation and micrometastasis generation of breast cancer cells within a bone-like microenvironment and demonstrates the potential value of microfluidic systems to better understand cancer biology and screen for new therapeutics.

Original languageEnglish
Pages (from-to)2454-2461
Number of pages8
JournalBiomaterials
Volume35
Issue number8
DOIs
Publication statusPublished - 2014 Mar

Bibliographical note

Funding Information:
Support from the National Cancer Institute ( R33 CA174550-01 and R21 CA140096 ) and the Italian Ministry of Health, fellowship support to S. Bersini provided by the Fondazione Fratelli Agostino and Enrico Rocca through the Progetto Rocca Doctoral Fellowship and support to J.S. Jeon provided by Repligen Fellowship in Cancer Research and Draper Fellowship are gratefully acknowledged. S. Chung was supported by NRF (2012-022481) and KETEP (20124010203250) of Korea. Appendix A

Keywords

  • Bone
  • Breast cancer
  • Extravasation
  • Hydrogel
  • Metastasis
  • Microfluidics

ASJC Scopus subject areas

  • Mechanics of Materials
  • Ceramics and Composites
  • Bioengineering
  • Biophysics
  • Biomaterials

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