Three-dimensional vascularized lung cancer-on-a-chip with lung extracellular matrix hydrogels for in vitro screening

Sangun Park, Tae Hee Kim, Soo Hyun Kim, Seungkwon You, Youngmee Jung

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microen-vironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool.

Original languageEnglish
Article number3930
JournalCancers
Volume13
Issue number16
DOIs
Publication statusPublished - 2021 Aug 2

Keywords

  • Angiogenesis
  • Cancer-on-a-chip
  • Decellularized extracellular matrix
  • Drug screening
  • Tumor microenvironment
  • Vascularization

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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