The tumor microenvironment (TME) is decisive for the eradication or survival of any tumor mass. Moreover, it plays a pivotal role for metastasis and for providing the metastatic niche. The TME offers special physiological conditions and is composed of, for example, surrounding blood vessels, the extracellular matrix (ECM), diverse signaling molecules, exosomes and several cell types including, but not being limited to, infiltrated immune cells, cancer-associated endothelial cells (CAEs), and cancer-associated fibroblasts (CAFs). These cells can additionally and significantly contribute to tumor and metastasis progression, especially also by acting via their own deregulated micro (mi) RNA expression or activity. Thus, miRNAs are essential players in the crosstalk between cancer cells and the TME. MiRNAs are small non-coding (nc) RNAs that typically inhibit translation and stability of messenger (m) RNAs, thus being able to regulate several cell functions including proliferation, migration, differentiation, survival, invasion, and several steps of the metastatic cascade. The dynamic interplay between miRNAs in different cell types or organelles such as exosomes, ECM macromolecules, and the TME plays critical roles in many aspects of cancer development. This chapter aims to give an overview on the multiple contributions of miRNAs as players within the TME, to summarize the role of miRNAs in the crosstalk between different cell populations found within the TME, and to illustrate how they act on tumorigenesis and the behavior of cells in the TME context. Lastly, the potential clinical utility of miRNAs for cancer therapy is discussed.
Keywords: CAF; CD4+; CD8+; Cancer; ECM; Exosomes; Hypoxia; Immune checkpoint; Metastasis; NK; T-reg; TAM; TIDC; Tumor microenvironment; miRNAs.