Endothelial exosomes promote tumor progression by reprogramming tumor-associated macrophages
A collaboration between several teams at the University of Liege has led to the discovery of a new function for exosomes in cancer progression. Exosomes, or extracellular vesicles (EVs) released by cells, are intercellular messengers that modify the tumor environment to promote breast cancer progression. Their results are published in the Journal of Extracellular Vesicles.
The evolution of a cancer as well as the response to treatment are strongly influenced by the microenvironment in which the tumor develops. Tumor cells interact with blood vessel cells (endothelial cells) but also with stromal cells such as fibroblasts or immune cells. Ingrid Struman's laboratory is interested in the strategies used by these cells to communicate. The work recently published in the Journal of Extracellular Vesicles shows that the cancer cell modifies the communication with the surrounding cells to its own advantage. Specifically, during tumor growth, endothelial cells release exosomes that in turn alter tumor immunity.
Exosomes are small extracellular vesicles (EVs) that are about 100 nanometers in size; they are inter-cellular messengers. In the context of cancer, tumor-derived EVs participate in tumor progression by deregulating various physiological processes, including angiogenesis and inflammation. Here we report that EVs released from endothelial cells in the environment of a breast tumor participate in the recruitment of macrophages to the tumor, leading to an immunomodulatory phenotype favorable to tumor growth. Using sequencing approaches, we identified several microRNAs present in endothelial cell EVs that share common targets involved in the regulation of the immune system.
The goal of this project was to better understand how breast cancer cells modify host cells to better progress. Beyond the understanding of the mechanism of action, this study opens new perspectives as it highlights new therapeutic targets to develop new treatments for this disease. Ingrid Struman's team will continue this work to better understand the mechanism involved in the export of microRNAs. She is also interested in the impact of this discovery on the spread of metastasis. These projects are the subject of a new project funded by Télévie, ULiège and FNRS.
This study is the result of a collaboration funded by an ARC of the ULiège and the FNRS between the teams of Pr. Franck Dequiedt and Dr. Ingrid Struman (Senior Research Fellow FNRS). This study was also carried out in collaboration with other GIGA researchers - the team of Souad Rahmouni (GIGA-Medical Genomics) and Dr. Julien Guiot (GIGA-I3 - Pneumology Department of the CHU).
Model of how endothelial EVs promote tumor progression by inducing M2-like polarization of TAMs. (1) In the presence of TME, ECs are activated and release EVs that contain several tumour-associated miRNAs, including miR-142-5p, miR-183-5p and miR-222-3p. (2) These modified EVs deliver miR-142-5p, miR-183-5p and miR-222-3p into TAMs and induce M2-like polarization. (3) An increased number of M2 TAMs promotes progression of the tumour