Tumor microenvironment in lung cancer-derived brain metastasis

Abstract

Brain metastasis (BM) is the leading cause of mortality in lung cancer patients. The process of BM (from initial primary tumor development, migration and intravasation, dissemination and survival in the bloodstream, extravasation, to colonization and growth to metastases) is a complex process for which few tumor cells complete the entire process. Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment (TME) in assisting tumor cells in the completion of each BM step. This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer. The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.

Figure 1

Schematic representation of the stages of the formation of LCBM and interactions between TME and tumor cells. ARID5A: AT-rich interaction domain 5A; Cx43: Connexin 43; ECM: Extracellular matrix; EMT: Epithelial-mesenchymal transition; FOSL2: Fos-like antigen 2; HDGF: Hepatoma-derived growth factor; HGF: Hepatocyte growth factor; hMENA: human mammalian ENA; IGF-1: Insulin-like growth factor 1; IL: Interleukin; LCBM: Lung cancer brain metastasis; MCM3AP-AS1: lncRNA MCM3AP antisense RNA 1; MIF: Migration inhibitory factor; miR: MicroRNA; MMP: Matrix metalloproteinases; MRTF: Myocardin-related transcription factor; NF-κB: Nuclear factor kappa-B; PA: Plasminogen activator; PAI-1: Plasminogen activator inhibitor-1; PCDH7: Pro-calmodulin 7; PD-L1: Programmed cell death-ligand 1; PFN2: Profilin 2; SDF-1: Stromal cell-derived factor-1; SIRT1: Sirtuin 1; SNAI1: Snail 1; TGF-β: Transforming growth factor-β; TIAM2: T-cell lymphoma invasion and metastasis 2; TME: Tumor microenvironment; TNF-α: Tumor necrosis factor-α; VEGF: Vascular endothelial growth factor; YAP: Yes-associated protein.