Publications by authors named "Fabien Bertillot"

Epithelial tumors are characterized by abundant inter- and intra-tumor heterogeneity, which complicates diagnostics and treatment. The contribution of cancer-stroma interactions to this heterogeneity is poorly understood. Here, we report a paradigm to quantify phenotypic diversity in head and neck squamous cell carcinoma (HNSCC) with single-cell resolution.

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Article Synopsis
  • * A comparison of non-cancerous and patient-derived VFC cells shows an association between cancer progression, reduction in specific cell adhesion proteins, and changes in how cells move collectively.
  • * Mimicking the normal mechanical activity of healthy tissue can reduce tumor-promoting factors, while a correlation was found between ECM content, a signaling protein (YAP), and patient survival, suggesting potential therapeutic strategies targeting these pathways.
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At the early stage of tumor progression, fibroblasts are located at the outer edges of the tumor, forming an encasing layer around it. In this work, we have developed a 3D in vitro model where fibroblasts' layout resembles the structure seen in carcinoma in situ. We use a microfluidic encapsulation technology to co-culture fibroblasts and cancer cells within hollow, permeable, and elastic alginate shells.

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Morphogenesis and cell state transitions must be coordinated in time and space to produce a functional tissue. An excellent paradigm to understand the coupling of these processes is mammalian hair follicle development, which is initiated by the formation of an epithelial invagination-termed placode-that coincides with the emergence of a designated hair follicle stem cell population. The mechanisms directing the deformation of the epithelium, cell state transitions and physical compartmentalization of the placode are unknown.

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Cells are continuously exposed to tissue-specific extrinsic forces that are counteracted by cell-intrinsic force generation through the actomyosin cytoskeleton and alterations in the material properties of various cellular components, including the nucleus. Forces impact nuclei both directly through inducing deformation, which is sensed by various mechanosensitive components of the nucleus, as well as indirectly through the actomyosin cytoskeleton and mechanosensitive pathways activated in the cytoplasm. To view this SnapShot, open or download the PDF.

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During tumor progression, cancer cells acquire the ability to escape the primary tumor and invade adjacent tissues. They migrate through the stroma to reach blood or lymphatics vessels that will allow them to disseminate throughout the body and form metastasis at distant organs. To assay invasion capacity of cells in vitro, multicellular spheroids of cancer cells, mimicking primary tumor, are commonly embedded in collagen I extracellular matrix, which mimics the stroma.

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Intracellular motion can be quantitatively monitored in tissues using coherence-gated microscopic techniques. With full-field optical coherence tomography (FFOCT), the use of high numerical aperture microscope objectives provides a high resolution mapping of intracellular dynamics that are probed with subwavelength sensitivity. In the upper temporal bandwidth that we have used (1-6 Hz) the main contribution to the dynamic signal arises from the overall dynamical, optically heterogeneous cytoplasm.

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