Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids

Venktesh S. Shirure, Ye Bi, Matthew B. Curtis, Andrew Lezia, Madeleine M. Goedegebuure, S. Peter Goedegebuure, Rebecca Aft, Ryan C. Fields, Steven George

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Most cancer treatment strategies target cell proliferation, angiogenesis, migration, and intravasation of tumor cells in an attempt to limit tumor growth and metastasis. An in vitro platform to assess tumor progression and drug sensitivity could provide avenues to enhance our understanding of tumor metastasis as well as precision medicine. We present a microfluidic platform that mimics biological mass transport near the arterial end of a capillary in the tumor microenvironment. A central feature is a quiescent perfused 3D microvascular network created prior to loading tumor cells or patient-derived tumor organoids in an adjacent compartment. The physiological delivery of nutrients and/or drugs to the tumor then occurs through the vascular network. We demonstrate the culture, growth, and treatment of tumor cell lines and patient-derived breast cancer organoids. The platform provides the opportunity to simultaneously and dynamically observe hallmark features of tumor progression including cell proliferation, angiogenesis, cell migration, and tumor cell intravasation. Additionally, primary breast tumor organoids are viable in the device for several weeks and induce robust sprouting angiogenesis. Finally, we demonstrate the feasibility of our platform for drug discovery and personalized medicine by analyzing the response to chemo- and anti-angiogenic therapy. Precision medicine-based cancer treatments can only be realized if individual tumors can be rapidly assessed for therapeutic sensitivity in a clinically relevant timeframe (⪅14 days). Our platform indicates that this goal can be achieved and provides compelling opportunities to advance precision medicine for cancer.

Original languageEnglish (US)
Pages (from-to)3687-3702
Number of pages16
JournalLab on a Chip
Volume18
Issue number23
DOIs
StatePublished - Dec 7 2018

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Organoids
Tumors
Cells
Cell Line
Pharmaceutical Preparations
Neoplasms
Precision Medicine
Medicine
Oncology
Cell proliferation
Biological Transport
Cell Proliferation
Breast Neoplasms
Neoplasm Metastasis
Therapeutics
Tumor Microenvironment
Microfluidics
Drug Discovery
Growth
Microvessels

ASJC Scopus subject areas

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

Cite this

Shirure, V. S., Bi, Y., Curtis, M. B., Lezia, A., Goedegebuure, M. M., Goedegebuure, S. P., ... George, S. (2018). Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids. Lab on a Chip, 18(23), 3687-3702. https://doi.org/10.1039/c8lc00596f

Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids. / Shirure, Venktesh S.; Bi, Ye; Curtis, Matthew B.; Lezia, Andrew; Goedegebuure, Madeleine M.; Goedegebuure, S. Peter; Aft, Rebecca; Fields, Ryan C.; George, Steven.

In: Lab on a Chip, Vol. 18, No. 23, 07.12.2018, p. 3687-3702.

Research output: Contribution to journalArticle

Shirure, VS, Bi, Y, Curtis, MB, Lezia, A, Goedegebuure, MM, Goedegebuure, SP, Aft, R, Fields, RC & George, S 2018, 'Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids', Lab on a Chip, vol. 18, no. 23, pp. 3687-3702. https://doi.org/10.1039/c8lc00596f
Shirure VS, Bi Y, Curtis MB, Lezia A, Goedegebuure MM, Goedegebuure SP et al. Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids. Lab on a Chip. 2018 Dec 7;18(23):3687-3702. https://doi.org/10.1039/c8lc00596f
Shirure, Venktesh S. ; Bi, Ye ; Curtis, Matthew B. ; Lezia, Andrew ; Goedegebuure, Madeleine M. ; Goedegebuure, S. Peter ; Aft, Rebecca ; Fields, Ryan C. ; George, Steven. / Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids. In: Lab on a Chip. 2018 ; Vol. 18, No. 23. pp. 3687-3702.
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