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Field Cancerization in NSCLC: A New Perspective on MicroRNAs in Macrophage Polarization

Journal

Publisher

MDPI
DOI: 10.3390/ijms22020746

Keywords

lung cancer; field cancerization; tumor microenvironment; macrophage polarization; miRNA

Funding

  1. Competitiveness Operational Program, 2014-2020 [35/01.09.2016, 103375]

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Lung cancer, particularly non-small cell lung cancer, is primarily caused by tobacco smoke which leads to progressive damage in the respiratory tract. The interactions between tumor cells, tumor microenvironment, and cancerized field involve molecular messages exchanged through various molecules like proteins, ncRNAs, and miRNAs. Understanding these interactions can provide insights into tumor regulatory mechanisms and potentially enhance therapy approaches for lung cancer.
Lung cancer is currently the first cause of cancer-related death. The major lung cancer subtype is non-small cell lung cancers (NSCLC), which accounts for approximatively 85% of cases. The major carcinogenic associated with lung cancer is tobacco smoke, which produces long-lasting and progressive damage to the respiratory tract. The progressive and diffuse alterations that occur in the respiratory tract of patients with cancer and premalignant lesions have been described as field cancerization. At the level of tumor cells, adjacent tumor microenvironment (TME) and cancerized field are taking place dynamic interactions through direct cell-to-cell communication or through extracellular vesicles. These molecular messages exchanged between tumor and nontumor cells are represented by proteins, noncoding RNAs (ncRNAs) and microRNAs (miRNAs). In this paper, we analyze the miRNA roles in the macrophage polarization at the level of TME and cancerized field in NSCLC. Identifying molecular players that can influence the phenotypic states at the level of malignant cells, tumor microenvironment and cancerized field can provide us new insights into tumor regulatory mechanisms that can be further modulated to restore the immunogenic capacity of the TME. This approach could revert alterations in the cancerized field and could enhance currently available therapy approaches.

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