Biology subjects

Barbazan, J.

Publications and source records attributed to Barbazan, J..

6 recordsLinked to original sources

bioRxiv2025

Bovine colostrum-derived extracellular vesicles impair cancer cell proliferation through transcriptional repression.

Milk-derived extracellular vesicles (EVs) are a promising source of molecules with therapeutic potential. Bovine colostrum is particularly enriched in EVs, which carry a unique cargo of proteins involved in immune regulation, development, and cellular signaling. However, despite promising bioactive effects in various fields, little is known about their potential as anti-cancer agents. Here, we demonstrate that colostrum-derived EVs (Col-EVs) exert a potent and specific anti-proliferative effect on gastrointestinal cancer cell lines, independent of apoptosis induction. Using a multi-modal approach combining proteomics and functional assays, we show that Col-EVs induce a reversible proliferative arrest through transcriptional repression and chromatin and nuclear remodeling. Col-EV treatment leads to widespread dysregulation of RNA processing and transcriptional machinery, including the downregulation of splicing factors and chromatin regulators essential for cell cycle progression. These molecular changes are accompanied by chromatin compaction, nuclear reorganization, and cytoskeletal remodeling. Notably, these effects do not induce cell death and are reversible upon EV removal, suggesting a modulatory mechanism rather than cytotoxicity. Furthermore, Col-EVs enhance the efficacy of DNA-targeting chemotherapies such as 5-fluorouracil, indicating their potential as adjunctive agents in cancer treatment. Overall, our findings reveal that Col-EVs can selectively and reversibly suppress cancer cell proliferation by reprogramming transcriptional and nuclear architecture, offering a natural, biocompatible strategy for modulating tumor growth and sensitizing cancer cells to conventional therapies.

cancer biology↗

bioRxiv2024

Friction-induced budding of a cancer cell monolayer

The environment surrounding a tumor plays a crucial role in cancer cell dissemination. Within this microenvironment, cancer-associated fibroblasts (CAFs) generate compressive forces and actively remodel tumors. Using in vitro circular clusters of cancer cell monolayers surrounded by CAFs, we generate structures that are reminiscent of multicellular buds observed in vivo for colo-rectal cancer. A supracellular contractile ring spontaneously assembles at the inner edge of the CAF monolayer and drives its closure on top of the cancer cells through a purse-string mechanism. The frictional shear stress exerted by CAFs triggers multilayering of cancer cells, followed by the emergence of a multicellular bud constricted by the CAF ring. To explain this observation, we developed a theoretical model based on continuum mechanics. This model outlines the early transformations in the shape of cancer cell monolayer and links the layering of cells to a general criterion involving height deformation. It identifies the specific physical conditions that favors budding, and reproduces the observed dependence of the budding probability and bud sizes with the diameter of the cancer cell cluster. Our findings highlight the importance of active mechanical interactions between the tumor and its micro-environment on aggressive modes of cancer invasion.

biophysics↗

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↗

bioRxiv2021

Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule is a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.

cell biology↗

bioRxiv2019

Centrosome amplification favours survival and impairs ovarian cancer progression

Centrosome amplification, the presence of more than two centrosomes in a cell is a common feature of most human cancer cell lines. However, little is known about centrosome numbers of human cancers and whether amplification or other numerical aberrations are frequently present. To address this question, we have analyzed a large cohort of human epithelial ovarian cancers (EOCs) from 100 patients. Using state-of-the-art microscopy, we have determined the Centrosome-Nucleus Index (CNI) of each tumor. We found that EOCs show infrequent centrosome amplifications. Strikingly, the large majority of these tumors presented low CNIs. We show that low CNI tumors are enriched in the mesenchymal subgroup and correlate with poor patient survival. Our findings highlight a novel paradigm linking low centrosome number with highly aggressive behavior in ovarian cancers and show that the CNI signature may be used to stratify ovarian cancers.

cancer biology↗

bioRxiv2018

Two Isoforms of the Guanine Nucleotide Exchange Factor, Daple/CCDC88C Cooperate as Tumor Suppressors

Previously Aznar et al., showed that Daple enables Wnt/Frizzled receptors to transactivate trimeric G proteins during non-canonical Wnt signaling via a novel G-protein binding and activating (GBA) motif. By doing so, Daple serves as a double-edged sword; earlier during oncogenesis it suppresses neoplastic transformation and tumor growth, but later it triggers epithelial messenchymal transition (EMT). We have identified and characterized two isoforms of the human Daple/CCDC88c gene. While both isoforms cooperatively suppress tumor growth via their GBA motif, only the full-length transcript triggers EMT and invasion. Aspirin suppresses the full-length transcript and protein but upregulates the short isoform. Both isoforms are suppressed during colon cancer progression, and their reduced expression carries additive prognostic significance. These findings provide insights into the opposing roles of Daple during cancer progression and define the G protein regulatory GBA motif as one of the minimal modules essential for Daples role as a tumor suppressor.

cancer biology↗