Tumor Microenvironment: Molecular Mechanisms and Signaling Pathways Involved in Metastatic Progression

© 2021 Link, Ilardi and Zannetti.
Despite important advances in cancer treatments, metastasis remains the major cause of cancer mortality. In the complex tumor microenvironment, several malignant and non-malignant cell types, as well as components of the extracellular matrix (ECM), interact together to promote the metastatic process (1, 2). Stromal cells, which are already present in the tumor microenvironment (TME), are recruited from distant sites and “educated” by cancer cells through a dynamic cross-talk involving growth factors, cytokines, chemokines, miRNAs, and exosomes (3, 4). These primed cells, including cancer-associated fibroblasts, tumor-associated mesenchymal stem cells, tumor-associated macrophages, and other immune cells acquire a pro-metastatic function that supports tumor cells in each step of the metastatic cascade (4). Importantly, the bi-directional communication between tumor microenvironment and cancer cells induces the epithelial-mesenchymal-transition (EMT) that in turn elicits profound morphological and functional changes in tumor cells, triggering a mesenchymal-like phenotype with higher invasive potential (5). A crucial step in the establishment of metastases includes the formation of a pre-metastatic niche where recruited stromal cells contribute to creating a favorable microenvironment that permits cancer cell seeding (6). To successfully germ in a distant site, cancer cells need to find nutrients, an ECM that can support their attachment, and stromal cells that help them with paracrine signaling to survive and proliferate in the new environment (1). Responding to this complex scenario, this Research Topic aims to bring together more recent studies and discoveries that shed light on the molecular mechanisms and signaling pathways involved in the cross-talk between TME and cancer cells. The special issue on the “Tumor Microenvironment: Molecular Mechanisms and Signaling Pathways Involved in Metastatic Progression” includes 27 original articles, 11 review articles, and three mini-review articles, each of which advances knowledge in this field concerning different types of carcinomas.
This work was supported by the Spanish Ministry of Science, Innovation, and Universities through Grant RTI2018-094629-B-I00 to WL. This work was supported by grants from from MIUR Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN) Bando 2017-grant 2017MHJJ55, MIUR-PON “Ricerca e Innovazione” 2014-2020 (grant MOLIMONCOBRAIN LAB), from Regione Campania PO FESR 2014-2020 (grant eMORFORAD) to AZ.