Inter-Spheroid Proximity and Matrix Remodeling Determine CAF-Mediated Cancer Cell Invasion DOI Creative Commons

Pranav Mehta,

Ankur Bordoloi, Cor J. Ravensbergen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Abstract Breast cancer is the most commonly diagnosed malignancy worldwide, with molecular subtypes following distinct clinical trajectories. While Luminal A breast cancers are typically indolent, a subset enriched in α-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs) exhibits aggressive behavior, facilitating tumor invasion. However, biophysical mechanisms by which CAFs drive invasion and extracellular matrix (ECM) remodeling remain unclear. Furthermore, temporal spatial dynamics of CAF interactions collagen cell spheroids unknown, raising question whether these processes follow deterministic sequence or occur stochastically. To address this, we conduct histological analysis tumors, revealing variation CAF, cell, ECM organization at boundaries. assess impact on invasion, use 3D in-vitro model co-embedding 19TT MCF7 luminal within three-dimensional (3D) collagen-I hydrogel perform time-lapse imaging. We demonstrate that inter-spheroid distance critically determines CAF-induced spheroid behavior. show CAF-mediated degradation precedes disruption critical promoting expansion dissemination. broad-spectrum metalloproteinase inhibition suppresses CAF-driven expansion, it does not prevent remodeling, migration, single-cell dissemination spheroids. complementary heterospheroid reveals similar despite altered cellular arrangement cells CAFs. These findings enhance our understanding relationship between activity promote providing insights into potential therapeutic benefits targeting treatment.

Язык: Английский

Inter-Spheroid Proximity and Matrix Remodeling Determine CAF-Mediated Cancer Cell Invasion DOI Creative Commons

Pranav Mehta,

Ankur Bordoloi, Cor J. Ravensbergen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Abstract Breast cancer is the most commonly diagnosed malignancy worldwide, with molecular subtypes following distinct clinical trajectories. While Luminal A breast cancers are typically indolent, a subset enriched in α-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs) exhibits aggressive behavior, facilitating tumor invasion. However, biophysical mechanisms by which CAFs drive invasion and extracellular matrix (ECM) remodeling remain unclear. Furthermore, temporal spatial dynamics of CAF interactions collagen cell spheroids unknown, raising question whether these processes follow deterministic sequence or occur stochastically. To address this, we conduct histological analysis tumors, revealing variation CAF, cell, ECM organization at boundaries. assess impact on invasion, use 3D in-vitro model co-embedding 19TT MCF7 luminal within three-dimensional (3D) collagen-I hydrogel perform time-lapse imaging. We demonstrate that inter-spheroid distance critically determines CAF-induced spheroid behavior. show CAF-mediated degradation precedes disruption critical promoting expansion dissemination. broad-spectrum metalloproteinase inhibition suppresses CAF-driven expansion, it does not prevent remodeling, migration, single-cell dissemination spheroids. complementary heterospheroid reveals similar despite altered cellular arrangement cells CAFs. These findings enhance our understanding relationship between activity promote providing insights into potential therapeutic benefits targeting treatment.

Язык: Английский

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