Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

Jessie S. Jeon, Simone Bersini, Mara Gilardi, Gabriele Dubini, Joseph L. Charest, Matteo Moretti, Roger D. Kamm

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into themyoblast-containingmatrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine.

Original languageEnglish
Pages (from-to)214-219
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number1
DOIs
Publication statusPublished - Jan 6 2015

Fingerprint

Microfluidics
Breast Neoplasms
Microvessels
Neoplasms
Adenosine A3 Receptors
Bone and Bones
Precision Medicine
Preclinical Drug Evaluations
Myoblasts
Adenosine
Permeability
Neoplasm Metastasis
Muscles

Keywords

  • Breast cancer
  • Extravasation
  • Metastasis
  • Microenvironment
  • Microfluidics

ASJC Scopus subject areas

  • General

Cite this

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. / Jeon, Jessie S.; Bersini, Simone; Gilardi, Mara; Dubini, Gabriele; Charest, Joseph L.; Moretti, Matteo; Kamm, Roger D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 1, 06.01.2015, p. 214-219.

Research output: Contribution to journalArticle

Jeon, Jessie S. ; Bersini, Simone ; Gilardi, Mara ; Dubini, Gabriele ; Charest, Joseph L. ; Moretti, Matteo ; Kamm, Roger D. / Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 1. pp. 214-219.
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