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Purpose <p>Cancer cell invasion into the stroma is a key step in tumor progression, yet many in vitro models fail to recapitulate stromal architecture or permit quantitative analysis along the thickness (Z) dimension. This study aimed to develop a simple 3D co-culture disc system that maintains fibroblast-rich gels without shrinkage and enables quantitative evaluation of epithelial cancer cell invasion.</p> Methods <p>A thin plastic disc with a central opening was used to support collagen gels containing normal human lung fibroblasts (NHLFs). Noncancerous MCF-10&#xa0;A and cancer cell lines with different invasive capacities (MCF-7, MDA-MB-231) were seeded on the gel surface. Gel contraction, fibroblast morphology, and invasion depth were assessed using fluorescence labeling and confocal laser scanning microscopy (CLSM). Transforming growth factor-β1 (TGF-β1) was applied to test responsiveness to environmental stimuli.</p> Results <p>Fibroblast-rich gels contracted uniaxially along the Z-axis but remained laterally stable within the disc, enabling long-term co-culture. Cancer cells showed distinct invasion profiles, with MDA-MB-231 invading significantly deeper than MCF-10&#xa0;A or MCF-7. Invading cells frequently localized near <i>αSMA</i>-high myofibroblast-like fibroblasts. TGF-β treatment increased fibroblast contractility and further enhanced cancer cell invasion, demonstrating that the system quantitatively detects stromal activation and invasion-promoting cues.</p> Conclusion <p>The disc-based 3D co-culture system offers a simple and physiologically relevant platform for quantifying cancer cell invasion and fibroblast activation. By supporting fibroblast-rich stromal environments, resolving Z-axis invasion, and responding to external stimuli such as TGF-β, this system provides a practical tool for studying tumor–stroma interactions and may be applicable to patient-derived cells in future studies.</p>

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3D in vitro co-culture disc for assessing cancer invasiveness in the tumor stroma microenvironment

  • 期刊论文

  • 发表日期：

    2026年2月17日

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  • Weiyou Sun,
  • Yutaka Kikuchi,
  • Haruko Takahashi

摘要

Purpose

Cancer cell invasion into the stroma is a key step in tumor progression, yet many in vitro models fail to recapitulate stromal architecture or permit quantitative analysis along the thickness (Z) dimension. This study aimed to develop a simple 3D co-culture disc system that maintains fibroblast-rich gels without shrinkage and enables quantitative evaluation of epithelial cancer cell invasion.

Methods

A thin plastic disc with a central opening was used to support collagen gels containing normal human lung fibroblasts (NHLFs). Noncancerous MCF-10 A and cancer cell lines with different invasive capacities (MCF-7, MDA-MB-231) were seeded on the gel surface. Gel contraction, fibroblast morphology, and invasion depth were assessed using fluorescence labeling and confocal laser scanning microscopy (CLSM). Transforming growth factor-β1 (TGF-β1) was applied to test responsiveness to environmental stimuli.

Results

Fibroblast-rich gels contracted uniaxially along the Z-axis but remained laterally stable within the disc, enabling long-term co-culture. Cancer cells showed distinct invasion profiles, with MDA-MB-231 invading significantly deeper than MCF-10 A or MCF-7. Invading cells frequently localized near αSMA-high myofibroblast-like fibroblasts. TGF-β treatment increased fibroblast contractility and further enhanced cancer cell invasion, demonstrating that the system quantitatively detects stromal activation and invasion-promoting cues.

Conclusion

The disc-based 3D co-culture system offers a simple and physiologically relevant platform for quantifying cancer cell invasion and fibroblast activation. By supporting fibroblast-rich stromal environments, resolving Z-axis invasion, and responding to external stimuli such as TGF-β, this system provides a practical tool for studying tumor–stroma interactions and may be applicable to patient-derived cells in future studies.