Title : Recellularized organs as ex vivo models for colorectal cancer metastasis
Abstract:
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The main factor leading to mortality is the development of metastasis, mostly occurring in the liver. Reasons why the liver is the main metastatic site for CRC and which factors lead to invasive and metastatic growth of the primary tumor in this specific organ remain unclear. Previous studies have suggested that stromal cells are involved in altering the extracellular matrix (ECM) in the tumor microenvironment because they play a major role in these processes. However, the underlying mechanisms and factors are still largely unknown.
Experimental set-ups to decrypt the complex in vivo mechanisms responsible for metastatic spread in human cancers are mainly based on xenogeneic in vivo experiments or artificial in vitro models. Both models suffer from methodical limitations and are not sufficient to mimic complex in vivo processes. The tissue engineering concept of decellularization and recellularization could overcome these limitations and lead to novel and complex ex vivo tumor models. During decellularization cells and antigenic material are removed from an organ and only the organ-specific ECM is conserved. Thus, we aim to establish recellularized organs as a model system for CRC metastasis to understand how the organ-specific ECM and tumor stromal cells i.e. bone marrow-derived macrophages (BMDMs) and bone marrow stromal cells (BMSCs) affect engraftment, invasiveness and malignant potency of CRC cells in the liver in order to identify and validate potential genes, proteins and signaling pathways which play key roles in the development of CRC liver metastasis. These in turn could be potential targets for novel therapeutic approaches.
