Abstract 5401: Vasculogenic mimicry: A three-step progress to form lumen-containing and fluid-conducting tubular structures in vitro

Abstract

Abstract Introduction: Vasculogenic mimicry (VM) is a clinical phenomenon by which cancer cells can form vessel-like structures in an endothelial-free (CD31-) fashion. VM presence in tumors correlates to poor patient prognosis. In our laboratory we have established an in vitro model where cancer cells from either cell lines or primary culture form lumen-lined and fluid-conducting tubular structures when grown on laminin-rich Matrigel over a four-day period. Given the duration of formation and the complexity of these structures, we hypothesize that VM in vitro is a multistep process, where each stage requires spatio-temporal organization of adhesive proteins, stemness and EMT (suggesting the need for epithelial to mesenchymal transition) signaling. Methods: Using our in vitro models, we analyzed by siRNA, immunostaining and live cell imaging with Airyscan the distinct phases and the corresponding spatio-temporal organization of selected proteins. Results: We show that VM in vitro has three distinct phases that are characterized by (1) alignment and migration, (2) contraction, proliferation and bridge formation, and (3) tubular structure closure and lumen formation. These steps require spatio-temporal distribution of ZEB1 and E-cadherin (suggesting gain and loss of epithelial to mesenchymal transition), the presence of Integrin β1 and laminin 111, and the distinct localization of Laminin and CD44. Conclusion: A better characterization of VM may lead to the identification of a clinically useful marker to predict poor patient prognosis and shed light on a druggable pathway to treat this subgroup of aggressive cancer. Citation Format: Gareth I. Owen, Nicolle Santander, Gabriel Mingo, Pamela Gonzalez, Valentina George, Nicole Babbitt, Alejandra Espinioza, Isidora Vega, Cristobal Canales, Carolina Ibañez, Roger Gejman, Juan Carlos Roa, Francisco Nualart, Andrea Ravasio, Cristina Bertocchi. Vasculogenic mimicry: A three-step progress to form lumen-containing and fluid-conducting tubular structures in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5401.