Biology subjects

Boche, A.

Publications and source records attributed to Boche, A..

5 recordsLinked to original sources

bioRxiv2025

The extracellular matrix dictates ovarian cancer cell migration in an in vivo-derived circulating environment

Ovarian cancer (OC) disseminates via ascites and interaction with peritoneal extracellular matrix (ECM). To dissect the crosstalk between ECM and ascites in OC cell migration, we developed an ovarian tumor-on-chip integrating OC tumor spheroids, perfusion-induced shear stress of fluid supplemented with key components of ascites or patient-derived ascites, and biomimetic ECMs mimicking either early-stage basement membrane or late-stage connective tissues. We evaluated the individual and combined effects of two key ascitic components, fibronectin and TGF-{beta}, and compared these results with the perfusion of patient ascites. Results showed that cell migration, morphology, and epithelial-to-mesenchymal transition (EMT) markers such as the reorganization of vimentin cytoskeleton depend strongly on ECM composition, regardless of biochemical cues. Fibronectin and TGF-{beta} synergistically enhanced migration and EMT signatures, especially on basement membrane-rich ECM. Patient ascites further promoted migration but did not override ECM-driven migration patterns. Our findings show that clinical ascites perfusion exemplifies the ECM-dependence of cancer cell migration. This highlights that ECM protein composition is a dominant regulator of OC cell migration, providing key insights for in vitro tumor modeling and therapeutic strategies targeting the metastatic microenvironment.

cancer biology↗

bioRxiv2024

Biomimetic Virus-Like Particles to control cell functions

Biomimetic cues from the extracellular matrix (ECM) are essential for optimizing cell microenvironments and biomaterials. While native ECM proteins or synthetic peptides offer potential solutions, challenges such as production cost, solubility, and conformational stability limit their use. Here, we present the development of virus-like particles (VLPs) derived from the AP205 RNA phage displaying peptides from key ECM proteins and evaluate their biological activity in a variety of assays. We show that our engineered VLPs can effectively stimulate cell adhesion, migration, proliferation and differentiation. By comparing focal adhesions formed by RGD VLPs with their parent protein, fibronectin, we elucidate both similarities and differences in cell interactions. In addition, we construct heterodimeric particles co-expressing RGD with differentiation peptides and demonstrate retention of bioactivity in a multi-peptide context. This study establishes AP205 VLPs as versatile nanoscale platforms capable of tuning cell functions, with promising applications in nanomedicine and biomaterials. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/612851v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@191b2c2org.highwire.dtl.DTLVardef@6edf5corg.highwire.dtl.DTLVardef@10a134aorg.highwire.dtl.DTLVardef@7864ef_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

bioengineering↗

bioRxiv2024

Hotwiring integrin endocytosis acutely modulates cell interactions

Integrins are heterodimeric cell surface receptors that govern cell-cell interactions, which in turn can influence multiscale processes: cell migration, extracellular matrix remodeling and tissue formation. These processes occur over timescales which range from milliseconds to days. While various strategies exist to study integrin function across biological scales from cell to tissue, they are often chronic and fail to target specific cell-cell interactions acutely. We engineered cells to rapidly alter cell behavior by downregulating the surface population of 5{beta}1 integrins through hot-wired clathrin-mediated endocytosis. This method allows for inducible, specific internalization of 5{beta}1 integrins, achieving acute downregulation across various cell lines in 5-30 minutes. We show that induced internalization of 5{beta}1 decreases the cell area, causes uptake of extracellular fibronectin, and decreases the rate of tumor spheroid compaction. This targeted control of multiscale processes by rapid downregulation of this important class of cell surface receptors demonstrates that hot-wired endocytosis is a useful tool to acutely modulate cell biology.

bioengineering↗

bioRxiv2024

Phenomics demonstrates cytokines additive induction of epithelial to mesenchymal transition

Epithelial to Mesenchymal Transition (EMT) is highly plastic with a program where cells lose adhesion and become more motile. EMT heterogeneity is one of the factors for disease progression and chemoresistance in cancer. Omics characterizations are costly and challenging to use. We developed single cell phenomics with easy to use wide-field fluorescence microscopy. We analyse over 70000 cells and combined 51 features. Our simplistic pipeline allows efficient tracking of EMT plasticity, with a single statistical metric. We discriminate four high EMT plasticity cancer cell lines along the EMT spectrum. We test two cytokines, inducing EMT in all cell lines, alone or in combination. The single cell EMT metrics demonstrate the additive effect of cytokines combination on EMT independently of cell line EMT spectrum. Single cell phenomics is uniquely suited to characterize the cellular heterogeneity in response to complex microenvironment, and show potential for drug testing assays.

cancer biology↗

bioRxiv2023

The balance between shear flow and extracellular matrix in ovarian cancer-on-chip

Ovarian cancer is the most lethal gynecologic cancer in developed countries. Silent onset of the metastatic activity of ovarian tumor cells is factor for poor outcomes. In the tumor microenvironment, the extracellular matrix (ECM) and flow shear stress are known to play key roles in directing cell invasion. Hence, acute and tunable tools are critical to mimic scaffold and fluid for building clinically relevant in vitro models. We have built an ovarian tumor-on-chip where tunable ECM models are easily seeded with tumor spheroids and integrated within a microfluidic chip. This allows the investigation of the crosstalk between the characteristics of the ECM models and shear stress on the migratory behavior and cellular heterogeneity of ovarian tumor cells. We vary the composition of the ECM playing with type I and IV collagens and laminin, and control the shear stress in the chip. This work shows that in the shear stress regime of the peritoneal cavity, the ECM plays a major role in driving individual or collective modes of migration. In the presence of basement membrane proteins, migration is more collective that on type I collagen regardless of shear stress level. In addition, with increasing shear stress, individual cell migration was enhanced, while no significant impact on collective migration could be measured. This highlights our ability to discriminate relevant parameters for onset and shifts of cell behavior using our in vitro models. Furthermore, we described the ability to shift cells from an epithelial phenotype to a more mesenchymal phenotype, which could allow us to describe the role of these parameters during epithelial-to-mesenchymal (EMT) transition as a continuous process. Finally, we conclude that the ECM should hold a central position in in vitro cancer models, to understand cell response and develop platforms for therapeutic development.

bioengineering↗