Extracellular matrix functions in lung cancer

Abstract Lung cancer is one of the most devastating types of malignant tumors, and a prime example of a chemical carcinogenesis-driven tumor entity. Lung cancer progression does not only depend on the presence of driver mutations within the cancer cells, but also on its interactions with the cellular and extracellular matrix environment. Genetic and epigenetic changes such as aberrant promoter methylation or altered expression of microRNAs cause the misexpression of collagens, laminins, proteoglycans, proteases and integrins in the tumor microenvironment. Associated signaling processes modulate the conversion of fibroblasts to contractile cancer-associated fibroblasts, tumor angiogenesis, escape from the immune system, and create a permissive niche for cancer stem cells. Protease-mediated digestion and posttranslational crosslinking of large matrix glycoproteins promote cancer cell motility by facilitating basement membrane penetration and by altering the stiffness of interstitial matrices. New therapeutic approaches utilizing specific matrix proteins as targets and tools for drug delivery have shown promising results in preclinical models of lung cancer.