Heterotypic 3D bioprinted tissues model tumor and tumor microenvironment phenotypes

 Webinar – Jueves 14 de mayo 16:00. Organizado por Lius 4 Cancer 

Link: https://conecta2.csic.es/b/nie-zk9-9fx 

“Heterotypic 3D bioprinted tissues model tumor and tumor microenvironment phenotypes” 

Prof. Ellen M. Langer. Oregon Health & Science University. 

The tumor microenvironment is composed of multiple cell types (e.g. fibroblast, vascular, and immune cells), extracellular matrix (ECM) proteins, and signaling molecules that critically influence tumor cell phenotypes. While the study of isolated tumor cells in culture has contributed to the discovery of oncogenes and tumor suppressors that regulate oncogenic phenotypes, the impact of the microenvironment and crosstalk between distinct cell types has been difficult to model. In order to understand how tumor-stromal cell and tumor-ECM interactions critically regulate tumor behaviors such as early tumor initiation, metastatic progression, and response to therapies, we recently developed heterotypic, scaffold-free tissue models of advanced cancer using an extrusion based bioprinter system. Multiple cell types including cancer cells, fibroblasts, endothelial cells, bone marrow-derived mesenchymal stem cells, and immune cells can be incorporated into bioprinted tissues with defined architecture. We found that cells within these structures exhibit a tissue-like cellular density, deposit ECM, and self-organize to form complex structures, as indicated by nascent endothelial networks. We can assess cell intrinsic, extrinsic, and spatial tumorigenic phenotypes including cell survival, cell proliferation, differentiation state, ECM deposition, and cellular migration within these tissues in response to extrinsic signals or therapies. Our current work is focused in three main areas: to understand signaling between tumor and stromal cell types in early cancer development that contribute to malignant tumor initiation, to understand the influence of fibroblast heterogeneity on tumor cell phenotypes, and to understand how the microenvironment influences therapeutic response. Together, our work demonstrates that bioprinted tumor tissues recapitulate many aspects of in vivo neoplastic tissues, and provide a manipulable model system to interrogate molecular mechanisms of tumor development, progression, and treatment response. 

Biography 

Prof. Ellen M. Langer is Research Assistant Professor at the Department of Molecular and Medical Genetics at Oregon Health & Science University. She is author of more than 20 papers in international peer review journals and 2 patents. Her primary research interest is to understand the molecular mechanisms underlying cellular plasticity during tumor initiation, response to therapy, and metastatic progression. Using 2D tissue culture, 3D bioprinted tissues, and mouse models, she is interrogating the cell-intrinsic and cell-extrinsic mechanisms by which tumor cells acquire or maintain the phenotypic heterogeneity that provides them with advantages in terms of growth, survival, drug resistance and metastasis.