A novel microfluidic model can mimic organ-specific metastasis of circulating tumor cells

Oncotarget. 2016 Nov 29;7(48):78421-78432. doi: 10.18632/oncotarget.9382.

Abstract

A biomimetic microsystem might compensate costly and time-consuming animal metastatic models. Herein we developed a biomimetic microfluidic model to study cancer metastasis. Primary cells isolated from different organs were cultured on the microlfuidic model to represent individual organs. Breast and salivary gland cancer cells were driven to flow over primary cell culture chambers, mimicking dynamic adhesion of circulating tumor cells (CTCs) to endothelium in vivo. These flowing artificial CTCs showed different metastatic potentials to lung on the microfluidic model. The traditional nude mouse model of lung metastasis was performed to investigate the physiological similarity of the microfluidic model to animal models. It was found that the metastatic potential of different cancer cells assessed by the microfluidic model was in agreement with that assessed by the nude mouse model. Furthermore, it was demonstrated that the metastatic inhibitor AMD3100 inhibited lung metastasis effectively in both the microfluidic model and the nude mouse model. Then the microfluidic model was used to mimick liver and bone metastasis of CTCs and confirm the potential for research of multiple-organ metastasis. Thus, the metastasis of CTCs to different organs was reconstituted on the microfluidic model. It may expand the capabilities of traditional cell culture models, providing a low-cost, time-saving, and rapid alternative to animal models.

Keywords: bionic model; circulating tumor cells; metastasis; microfluidic; multi-organ.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Benzylamines
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Adhesion
  • Cell Movement* / drug effects
  • Chemokines / metabolism
  • Coculture Techniques
  • Cyclams
  • Female
  • Heterocyclic Compounds / pharmacology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lab-On-A-Chip Devices*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary*
  • MCF-7 Cells
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microfluidic Analytical Techniques / instrumentation*
  • Neoplasm Invasiveness
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology*
  • Organ Specificity
  • Primary Cell Culture
  • Rats, Sprague-Dawley
  • Salivary Gland Neoplasms / drug therapy
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / pathology*
  • Time Factors

Substances

  • Antineoplastic Agents
  • Benzylamines
  • Chemokines
  • Cyclams
  • Heterocyclic Compounds
  • plerixafor