Olalde, B. | Search bioRxiv

bioRxiv2025

Stiffness and Viscoelasticity of Adipose Tissue Decellularized Extracellular Matrix Hydrogels Influence Proliferation, Growth Pattern, Migration and Invasion of Breast Cancer Cells

Breast cancer remains the leading cause of cancer-related mortality among women. Cellular behavior is influenced by the physicochemical factors of the extracellular matrix (ECM) surrounding them. In order to model the breast ECM, adipose tissue decellularized extracellular matrix (dECM)-derived hydrogels are generated, which retain the full biochemical complexity of the source tissue, while also exhibiting stiffness and viscoelastic properties comparable to those of breast tissue. By recapitulating the characteristics of their native environment, validated through proteomic analysis and rheology, the poorly metastatic MCF-7 and the highly invasive MDA-MB-231 breast cancer cell lines exhibit their archetypal behaviors within the 3D hydrogels. Moreover, these cells display significantly distinct proliferation, invasion, and growth patterns in hydrogels with different stiffness and viscoelasticity, highlighting the importance of biophysical parameters in modulating cell phenotype. These results illustrate that user-friendly 3D biomaterial models based on adipose tissue dECM can effectively replicate crucial aspects of in vivo cellular behavior. Table of ContentsThis study presents 3D hydrogels derived from porcine adipose tissue dECM that mimic biophysical and biochemical properties of breast tissue. Two breast cancer cell lines mimicking luminal and triple-negative subtypes, exhibited distinct proliferation, migration, and invasion behaviors depending on hydrogel stiffness and viscoelasticity. The results highlight how biophysical cues shape cell phenotype in a user-friendly 3D model. O_FIG O_LINKSMALLFIG WIDTH=179 HEIGHT=200 SRC="FIGDIR/small/693682v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@d0216eorg.highwire.dtl.DTLVardef@42c45borg.highwire.dtl.DTLVardef@1693385org.highwire.dtl.DTLVardef@1b598e1_HPS_FORMAT_FIGEXP M_FIG Created with Biorender.com C_FIG

bioengineering↗

bioRxiv2025

Single cell-derived spheroids for real-time growth and metabolomic studies in breast cancer

Breast cancer remains a leading cause of cancer-related mortality, with disease progression and metastasis posing significant challenges in treatment. Three-dimensional (3D) cancer models have emerged as valuable tools for studying cancer cell biology in a physiologically relevant microenvironment. Studying the tumour heterogeneity and metabolic adaptations at the single-cell level can be crucial to identify factors driving metastatic progression. Here, we present a novel approach to generate single cell-derived breast cancer spheroids using cell lines (MCF-7 and MCF-10A) within a decellularised adipose tissue extracellular matrix (adECM). Spheroid culture conditions were optimised with integrated plasmonic nanosensors (gold nanostars - GNSs), to enable real-time surface-enhanced Raman scattering (SERS)-based measurements. Our results demonstrated that spheroid growth kinetics and viability in adECM were comparable to commonly used animal-derived matrices, validating its use as a reproducible ECM hydrogel. We further show that the concentration of plasmonic nanosensors used was compatible with cell culture and enabled SERS detection of a model reporter, paving the way for label-free, non-destructive analysis of cancer cell metabolism. This platform offers a promising approach to study cancer progression, including metabolic adaptations, with potential applications in biomarker discovery and preclinical research.

cancer biology↗