Deciphering the role of matrisome genes in 32 tumors. Focusing on the role of the extracellular matrix in acute myeloid leukemia and collagen XVIII in normal and leukemic hematopoiesis.

The tissue microenvironment: cells, soluble factors and the extracellular matrix (ECM), plays an enormous role in the various aspects of neoplastic transformation, tumor growth and metastatic dissemination. The idea that neoplasia actively models the composition of ECM molecules, globally referred to as the matrisome, is currently an established concept. Despite its importance, evidence of the role played by neoplastic cells in modifying their matrisome is still scarce and fragmented, and our work aims at providing a more systematic view of tumor ECM composition, especially in acute myeloid leukemia (AML). Using bioinformatics modeling and data from available cohorts, our work has provided an integrated view of ECM regulation in many types of tumors.

In analysis focusing on AML, ECM regulation also shows its intimate connection with patient prognosis and survival. Following our bioinformatic findings, we identified a downregulation of ECM molecule collagen XVIII in AML. Our mouse model confirmed that collagen XVIII is essential at maintaining homeostasis in the bone marrow (BM). The lack of collagen XVIII has an impact on blood cell lines, the vascular network of the BM and specific extra-medullar organs.

Concordant knowledge of the neoplastic ECM increases understanding of the development and behavior of different tumors. In addition, unraveling the role of the ECM in neoplasms may create new therapeutic opportunities against cancer.