HMGB1 Induce Lung Cancer By Promoting Cancer Cell Progress And Inhibiting Immunocytes’ Function

Abstract

The high-mobility group box 1 (HMGB1) protein is a highly conserved nuclear protein, that plays an important role in tumorigenesis and development of cancer cells; however, its exact mechanism remains to be elucidated. In this study, we found that HMGB1 endogenously expressed in Lewis lung cancer cells can promote proliferation of these cells. However, when Lewis cell lysates were introduced to immune cells, HMGB1 in tumor cell lysates (TCL) was found to have immunosuppressive effects, such as inducing apoptosis and inhibiting cytokine secretion. This inhibitory effect was found to be weakened after removing HMGB1 from TCL. Signal transduction pathway studies have shown that HMGB1 in TCL can inhibit the NF-кB signaling pathway in immune cells. It can also downregulate the expression of NF-кB, MMP-9, Bcl-2, and other cell-activating factors and simultaneously promote the expression of apoptosis-inducing factor Casp9. However, endogenous HMGB1 has the opposite effect on these signal transduction molecules in Lewis lung cancer cells. In summary, HMGB1 endogenously expressed in Lewis lung cancer cells can promote the proliferation of tumor cells, but the release of HMGB1 from necrotic and ruptured tumor cells induces immune cell apoptosis and functional inhibition. This enables HMGB1 to promote tumorigenesis while protecting cancer cells from attack by immune cells, thereby creating a microenvironment conducive to the growth of lung cancer cells. This induction of tumorigenesis is related to the activation of the NF-кB signaling pathway in tumor or immune cells in different ways.