Biology subjects

Visani, A.

Publications and source records attributed to Visani, A..

3 recordsLinked to original sources

bioRxiv2026

CXCL-CXCR2 signaling drives cancer-endothelium interactions in SCLC metastatic seeding

Small cell lung cancer (SCLC) is a highly metastatic malignancy with tropism to the liver, yet the signals that enable organ-specific metastatic colonization remain largely undefined. During metastasis, disseminated cancer cells first encounter endothelial cells (ECs) at the vascular-tissue interface, positioning cancer-endothelium crosstalk as a key determinant of metastatic success. Defining the signaling pathways underlying this reciprocal communication may uncover actionable vulnerabilities for preventing and treating this lethal disease. Here, we uncover an EC-derived CXCL chemokine program that activates cancer-intrinsic CXCR2-RAC1 signaling as a critical mediator of SCLC liver metastasis. By integrating in vitro and in vivo models, we show that SCLC cells induce robust CXCL chemokine expression from liver ECs, which in turn enhances SCLC migration and reinforces cancer cell-EC interactions. We applied highly quantitative metastatic colony barcode sequencing coupled with individual gene inactivation to demonstrate that CXCR2 is essential for SCLC migration and liver metastatic seeding. Mechanistically, CXCL-CXCR2 signaling activates RAC1-dependent F-actin assembling to drive SCLC motility during CXCL-induced metastatic seeding. Pharmacologic inhibition of CXCR2 or RAC1 suppresses SCLC migration and prevents SCLC liver metastasis. Together, our research defined a chemokine-driven signaling circuit that governs cancer-endothelium communication during the metastatic cascade and nominate the CXCL-CXCR2-RAC1 axis as a promising therapeutic vulnerability for preventing and treating metastatic SCLC.

cancer biology↗

bioRxiv2026

Quantitative dissection of the metastatic cascade at single colony resolution

Metastasis is the leading cause of cancer-related deaths. However, the core determinants and mechanistic principles underlying the metastatic cascade remain elusive. Small cell lung cancer (SCLC) is a highly aggressive malignancy with exceptional metastatic potential and limited therapeutic options. Here, we present Metastasis Originated Barcode Sequencing (MOBA-seq), a high-throughput in vivo platform that systematically maps genetic regulators across the metastatic cascade at single-colony resolution. MOBA-seq integrates scalable barcode-based lineage tracing with a computational pipeline that quantitatively deconvolutes genotype-specific effects on metastatic seeding, dormancy, and clonal expansion across hundreds of thousands of metastatic events. Applying this approach to more than 400 candidate regulators of SCLC, we uncovered tissue-specific metastatic suppressors and universal metastatic essential genes. We identified metastatic seeding as the predominant determinant of metastasis. Comparative analysis across recipient mice of distinct genetic backgrounds further revealed that innate immune surveillance constrains metastatic progression by reducing metastatic seeding and enforcing dormancy, with additional modulation by sex and tissue context. We validated the frequently mutated gene CREBBP as a key metastasis suppressor whose loss enhances SCLC metastasis through both tumor-intrinsic and immune-modulatory mechanisms. This work establishes a scalable and quantitative platform for mapping the metastatic fitness landscape at single-colony resolution across hundreds of thousands of in vivo data points. Our approach offers a broadly applicable framework for dissecting the interactions between cancer-intrinsic and microenvironmental factors governing tumor initiation, progression, and therapeutic response.

cancer biology↗

bioRxiv2024

RELATIONSHIP BETWEEN ACTUAL STRESS AND IN SITU MORPHOLOGICAL CHANGES IN THE MECHANICAL BEHAVIOR OF BIOMIMETIC POROUS HIERARCHICAL SCAFFOLDS

This study investigates the evolution with strain of the material volume fraction (i.e., porosity) and geometry in porous scaffolds to obtain a more accurate description of their stress-strain behavior. Single bundles and hierarchical structures (8 bundles enveloped by a membrane) were produced by electrospinning as tendon/ligament scaffolds. They underwent a micro-tomography in situ tensile test. Apparent and net stress were obtained using the initial sample cross-section and material volume fraction to normalize axial force. Micro-tomography revealed sample morphology change with strain to calculate the actual stress-strain. Moreover, nanofibers arrangement was revealed by scanning electron microscopy on both bundles and membranes. The description of the mechanical response significantly changed using evolving morphometry (actual stress-strain) instead of initial static one (apparent stress-strain), for both single bundle and hierarchical structure. The actual elastic modulus of the single bundles (583{+/-}97 MPa) was statistically higher than that of the hierarchical structures (163{+/-}107 MPa). This is related to the membrane, membrane-bundle and inter-bundle interactions. In the hierarchical structure, portions of the material resisting traction are constituted by nanofibers not aligned with the load. The different definitions for the stress-strain behavior allow different accuracy levels depending on the experimental complexity. The evolution of morphology with deformation can significantly affect the description of the mechanical response of porous scaffolds. This has a double impact in practical applications: at the body scale, it allows a better comparison between the scaffold behavior and the target tissue; at the cellular scale, it predicts the actual substrate stiffness that cells will face. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/630537v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@5d5337org.highwire.dtl.DTLVardef@1027047org.highwire.dtl.DTLVardef@11966a9org.highwire.dtl.DTLVardef@a2e4e3_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗