A mammary-specific microfluidic device for studying post-radiotherapy vascular-immune cell interactions

Abstract

Radiotherapy (RT) significantly improves outcomes and reduces the risk of recurrence in breast cancer. However, in patients that experience recurrence despite treatment, the irradiated breast tissue may create a pre-metastatic niche that promotes tumor cell infiltration. Because current models of metastasis lack key physiological and microenvironmental cues, we developed a mammary vasculature-on-chip (MVoC) to model how the vasculature responds to RT and impacts immune and tumor cell behavior in mammary tissue. Murine and human MVoCs incorporated endothelial cells (ECs) cultured under physiologic shear stress and mammary-specific fibroblasts to mimic the vascular-fibrous stroma interface. MVoCs exhibited a transient, acute response to RT that led to a persistent phenotypic shift. Neutrophils, which play key roles in pre-metastatic niche formation, adhered more to irradiated ECs and induced persistent damage to the endothelial barrier, preventing recovery. Neutrophils also significantly increased tumor cell adhesion to the endothelium in MVoCs. These findings demonstrate that MVoCs can be used to study RT-induced pre-metastatic niche formation and suggest a positive feedback loop between damaged ECs and immune cell activation that may facilitate tumor cell colonization. MVoCs provide a biologically relevant approach to probe molecular and cellular interactions, improving translation toward developing novel therapies that improve patient outcomes.

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BibTeX RIS

BibTeX

@misc{martello2026mammaryspecific,
  title = {{A mammary-specific microfluidic device for studying post-radiotherapy vascular-immune cell interactions}},
  author = {S. E. Martello and S. N. Luna and K. Derr and G. Martinez Franco and M. Paul and M. Mc Veigh and L. M. Bellan and M. Rafat},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.03.749257},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749257v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - A mammary-specific microfluidic device for studying post-radiotherapy vascular-immune cell interactions
AU  - S. E. Martello
AU  - S. N. Luna
AU  - K. Derr
AU  - G. Martinez Franco
AU  - M. Paul
AU  - M. Mc Veigh
AU  - L. M. Bellan
AU  - M. Rafat
PY  - 2026
DA  - 2026/09/03
PB  - bioRxiv
DO  - 10.64898/2026.09.03.749257
UR  - https://www.biorxiv.org/content/10.64898/2026.09.03.749257v1
AB  - Radiotherapy (RT) significantly improves outcomes and reduces the risk of recurrence in breast cancer. However, in patients that experience recurrence despite treatment, the irradiated breast tissue may create a pre-metastatic niche that promotes tumor cell infiltration. Because current models of metastasis lack key physiological and microenvironmental cues, we developed a mammary vasculature-on-chip (MVoC) to model how the vasculature responds to RT and impacts immune and tumor cell behavior in mammary tissue. Murine and human MVoCs incorporated endothelial cells (ECs) cultured under physiologic shear stress and mammary-specific fibroblasts to mimic the vascular-fibrous stroma interface. MVoCs exhibited a transient, acute response to RT that led to a persistent phenotypic shift. Neutrophils, which play key roles in pre-metastatic niche formation, adhered more to irradiated ECs and induced persistent damage to the endothelial barrier, preventing recovery. Neutrophils also significantly increased tumor cell adhesion to the endothelium in MVoCs. These findings demonstrate that MVoCs can be used to study RT-induced pre-metastatic niche formation and suggest a positive feedback loop between damaged ECs and immune cell activation that may facilitate tumor cell colonization. MVoCs provide a biologically relevant approach to probe molecular and cellular interactions, improving translation toward developing novel therapies that improve patient outcomes.
ER  -

Abstract

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