Microfluidic Tumor–Vascular Model to Study Breast Cancer Cell Invasion and Intravasation

Supriya Nagaraju, Danh Truong, Ghassan Mouneimne, Mehdi Nikkhah

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Cancer is a major leading cause of disease-related death in the world. The severe impact of cancer can be attributed to poor understanding of the mechanisms involved in earliest steps of the metastatic cascade, specifically invasion into the surrounding stroma and intravasation into the blood capillaries. However, conducting integrated biological studies of invasion and intravasation have been challenging, within in vivo models and traditional in vitro assay, due to difficulties in establishing a precise tumor microenvironment. To that end, in this work, a novel 3D microfluidic platform comprised of concentric three-layer cell-laden hydrogels for simultaneous investigation of breast cancer cell invasion and intravasation as well as vasculature maturation influenced by tumor–vascular crosstalk is developed. It was demonstrated that the presence of spontaneously formed vasculature enhance MDA-MB-231 invasion into the 3D stroma. Following invasion, cancer cells are visualized intravasating into the outer vasculature. Additionally, invading cancer cells significantly reduce vessel diameter while increasing permeability, consistent with previous in vivo studies. Major signaling cytokines involved in tumor–vascular crosstalk that govern cancer cell invasion and intravasation are further identified. Taken together, this platform will enable unique insights of critical biological events within the metastatic cascade, with significant potential for developing efficient cancer therapeutics.

Original languageEnglish (US)
Article number1701257
JournalAdvanced Healthcare Materials
Volume7
Issue number9
DOIs
StatePublished - May 9 2018

Keywords

  • cancer metastasis
  • intravasation
  • microfluidics
  • tumor microenvironment
  • tumor models

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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