Mechanobiology of lung cancer: effects of matrix stiffness on PD-L1 expression

抄録

Mechanical cues such as stretch, shear stress and matrix stiffness are considered to be involved in the mechanisms underlying the pathogenesis of pulmonary diseases. Because the elastic modulus of solid tumors (20-30 kPa) is much stiffer than that of normal lung parenchyma (0.5-5 kPa), the increased rigidity of the extracellular matrix (ECM) is one of characteristics of malignant phenotypes in solid tumors including lung cancer. Expression of programmed death-ligand 1 (PD-L1) in lung cancer cells regulates evasion of an immune check point system. We evaluated the effects of substrate stiffness on PD-L1 expression by using polyacrylamide hydrogels with different stiffnesses. We demonstrated that a stiff substrate enhanced PD-L1 expression via actin-dependent mechanisms in lung cancer cells. It is suggested that stiff substrates corresponding to pathologically cancer-related fibrotic tissues as a tumor environment regulates PD-L1 expression, which leads to evasion of the immune system and tumor growth.