Biology subjects

Baschieri, F.

Publications and source records attributed to Baschieri, F..

3 recordsLinked to original sources

bioRxiv2026

Ex Vivo Assay for Organ-Specific Cancer Cell Invasion

BackgroundMetastasis is the leading cause of cancer-related mortality, yet experimental models often fail to recapitulate the tissue-specific microenvironments that shape metastatic dissemination. While in vivo systems provide physiological relevance, they are poorly suited for mechanistic studies. Conversely, conventional in vitro assays lack the organ-specific extracellular matrix (ECM) context that critically regulates invasive behavior. There is therefore a need for accessible models that balance biological relevance with experimental feasibility. ResultsIn this study, we developed an ex vivo invasion platform based on mild detergent decellularization of mouse organs followed by vibratome slicing. This approach generates optically transparent lung, liver, and intestine ECM scaffolds that preserve native matrix architecture, mechanical properties, and retain biochemical hallmarks of their tissues of origin. Organ-derived matrices were integrated into standard microfluidic channels and analyzed using conventional fluorescence microscopy to enable quantitative assessment of cancer cell invasion. Benchmarking with breast cancer cell lines of defined invasive capacity, we could demonstrate the robustness and biological relevance of the system. Non-invasive MCF7 cells failed to infiltrate any organ scaffold, whereas highly invasive MDA-MB-231 cells exhibited pronounced organ-specific invasion. These cells preferentially invaded lung and liver ECM while showing minimal invasion of intestinal scaffolds, recapitulating clinically observed metastatic tropism. Quantitative invasion rates closely matched values previously reported in vivo using intravital microscopy. ConclusionsThis ex vivo organ-derived ECM platform provides a scalable, cost-effective, and experimentally accessible system to study ECM-driven determinants of metastatic invasion. By preserving tissue-specific matrix cues while reducing reliance on animal models, this approach provides a powerful tool to interrogate ECM-driven determinants of metastasis and to evaluate potential therapeutic interventions.

cancer biology↗

bioRxiv2022

Fibroblasts generate topographical cues that steer cancer cell migration

Fibroblasts play a fundamental role in tumor development. Among other functions, they regulate cancer cells migration through rearranging the extracellular matrix, secreting soluble factors and establishing direct physical contacts with cancer cells. Here, we report that migrating fibroblasts deposit on the substrate a network of tubular structures that serves as guidance cue for cancer cell migration. Such membranous tubular network, hereafter called tracks, is stably anchored to the substrate in a {beta}5 integrin-dependent manner. We found that cancer cells specifically adhere to tracks by using clathrin-coated structures that pinch and engulf tracks. Tracks represent thus a spatial memory of fibroblast migration paths that is read and erased by cancer cells directionally migrating along them. We propose that fibroblast tracks represent a topography-based intercellular communication system capable of steering cancer cells migration. TEASERThe migration path of fibroblasts is marked by tubules that act as railways to direct following cancer cell migration.

cancer biology↗

bioRxiv2019

Endocytosis frustration potentiates compression-induced receptor signaling

Cells experience mechanical stresses in different physiological and pathological settings. Clathrin-coated structures (CCSs) are sensitive to such perturbations in a way that often results in a mechanical impairment of their capacity to bud, ultimately impairing endocytosis. Compressive stress is a particular mechanical perturbation that leads to increased membrane tension and promotes proliferative signals. Here, we report that compression leads to CCSs frustration and that CCSs are required to potentiate receptor-mediated signaling in these conditions. We first confirmed that pressure stalls CCSs dynamics and showed that it also slows down the dynamic exchange of CCSs building blocks. As previously reported, compression-induced paracrine activation of the epidermal growth factor receptor (EGFR) was the primary cause of ERK activation in these conditions. We observed that the EGFR was efficiently recruited at CCSs upon compression and that CCSs were required for full ERK activation. In addition, we demonstrated that compression-induced frustrated CCSs could also serve as signaling platforms for the hepatocyte growth factor receptor (HGFR), provided HGF was present in the medium. We thus propose that, besides the particular case of EGFR paracrine activation, CCS frustration resulting from mechanical perturbations can potentiate signaling through different receptors with potential important consequences on cell adaptation to its environment.

cell biology↗