<p>Tumor cell–vasculature interactions play a crucial role in lung cancer progression and metastasis; however, traditional cell culture models rarely capture these complex dynamics. We developed a vascularized lung cancer organoid (VLCO) model by coculturing lung cancer organoids (LCOs) with blood vessel organoids (BVOs) to recreate the tumor–vasculature niche in a three-dimensional in vitro system. During coculture, LCOs migrated along BVO-formed vascular networks and invaded vessel-like structures, mimicking intravasation. The organoid types interacted via secretory factors, including TGF-β and PDGF-BB, inducing epithelial–mesenchymal transition (EMT) in LCOs and pericyte-to-fibroblast transition in BVOs. We also developed a scalable drug response assay for vasculature-induced EMT, enabling targeted therapeutic screening. The VLCO model provides a robust platform for studying tumor–endothelial crosstalk and testing antimetastatic therapies targeting tumor–vasculature interactions.</p>

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Modeling the metastatic tumor microenvironment: a co-culture platform of lung cancer and blood vessel organoids for drug evaluation

  • Mingyun Lee,
  • Yeo-Joon Yoon,
  • Ji Yeon Lee,
  • Mina Hwang,
  • Sewon Park,
  • Min Hak Lee,
  • Sang-Won Um,
  • Byoung Chul Cho,
  • Jinguen Rheey,
  • Toshiro Sato,
  • Yong Soo Lee

摘要

Tumor cell–vasculature interactions play a crucial role in lung cancer progression and metastasis; however, traditional cell culture models rarely capture these complex dynamics. We developed a vascularized lung cancer organoid (VLCO) model by coculturing lung cancer organoids (LCOs) with blood vessel organoids (BVOs) to recreate the tumor–vasculature niche in a three-dimensional in vitro system. During coculture, LCOs migrated along BVO-formed vascular networks and invaded vessel-like structures, mimicking intravasation. The organoid types interacted via secretory factors, including TGF-β and PDGF-BB, inducing epithelial–mesenchymal transition (EMT) in LCOs and pericyte-to-fibroblast transition in BVOs. We also developed a scalable drug response assay for vasculature-induced EMT, enabling targeted therapeutic screening. The VLCO model provides a robust platform for studying tumor–endothelial crosstalk and testing antimetastatic therapies targeting tumor–vasculature interactions.