Integration of intra- and extravasation in one cell-based microfluidic chip for the study of cancer metastasis

Min Kyeong Shin, Sung Kyu Kim, Hyungil Jung

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Most studies of cancer metastasis focus on cancer cell invasion utilizing adhesion assays that are performed independently, and are thus limited in their ability to mimic complex cancer metastasis on a chip. Here we report the development of an integrated cell-based microfluidic chip for intra- and extravasation that combines two assays on one chip for the study of the complex cascade of cancer metastasis. This device consists of two parts; one is an intravasation chamber for the three-dimensional (3-D) culture of cancer cells using a Matrigel matrix, and the other is an extravasation chamber for the detection of metastasized cancer cells by adhesion molecules expressed by epithelial cells. In this novel system, the intravasation and extravasation processes of cancer metastasis can be studied simultaneously using four screw valves. Metastatic LOVO and non-metastatic SW480 cells were used in this study, and the invasion of LOVOs was found to be higher compared to SW480. In contrast, invasion of cells treated with metalloproteinase (MMP) inhibitors decreased within the intravasation chamber. Degraded cancer cells from the intravasation chamber were detected within the extravasation chamber under physiological conditions of shear stress, and differences in binding efficiency were also detected when CA19-9 antibody, an inhibitor of cancer cell adhesion, was used to treat degraded cancer cells. Our results support the potential usefulness of this new 3D cell-based microfluidic system as a drug screening tool to select targets for the development of new drugs and to verify their effectiveness.

Original languageEnglish
Pages (from-to)3880-3887
Number of pages8
JournalLab on a Chip
Volume11
Issue number22
DOIs
Publication statusPublished - 2011 Nov 21

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Microfluidics
Cells
Neoplasm Metastasis
Assays
Neoplasms
Adhesion
Matrix Metalloproteinase Inhibitors
Cell adhesion
Cell Adhesion Molecules
Metalloproteases
Cell culture
Pharmaceutical Preparations
Shear stress
Screening
Antibodies
Preclinical Drug Evaluations
Molecules
Cell Adhesion
Cell Culture Techniques
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

Cite this

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abstract = "Most studies of cancer metastasis focus on cancer cell invasion utilizing adhesion assays that are performed independently, and are thus limited in their ability to mimic complex cancer metastasis on a chip. Here we report the development of an integrated cell-based microfluidic chip for intra- and extravasation that combines two assays on one chip for the study of the complex cascade of cancer metastasis. This device consists of two parts; one is an intravasation chamber for the three-dimensional (3-D) culture of cancer cells using a Matrigel matrix, and the other is an extravasation chamber for the detection of metastasized cancer cells by adhesion molecules expressed by epithelial cells. In this novel system, the intravasation and extravasation processes of cancer metastasis can be studied simultaneously using four screw valves. Metastatic LOVO and non-metastatic SW480 cells were used in this study, and the invasion of LOVOs was found to be higher compared to SW480. In contrast, invasion of cells treated with metalloproteinase (MMP) inhibitors decreased within the intravasation chamber. Degraded cancer cells from the intravasation chamber were detected within the extravasation chamber under physiological conditions of shear stress, and differences in binding efficiency were also detected when CA19-9 antibody, an inhibitor of cancer cell adhesion, was used to treat degraded cancer cells. Our results support the potential usefulness of this new 3D cell-based microfluidic system as a drug screening tool to select targets for the development of new drugs and to verify their effectiveness.",
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Integration of intra- and extravasation in one cell-based microfluidic chip for the study of cancer metastasis. / Shin, Min Kyeong; Kim, Sung Kyu; Jung, Hyungil.

In: Lab on a Chip, Vol. 11, No. 22, 21.11.2011, p. 3880-3887.

Research output: Contribution to journalArticle

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