Inflammatory Environment Promotes the Adhesion of Tumor Cells to Brain Microvascular Endothelial Cells

Abstract

Cancer patients usually suffer from unfavorable prognosis, particularly with the occurrence of brain metastasis of lung cancer. The key incident of brain metastasis initiation is crossing of blood-brain barrier (BBB) by cancer cells. Although preventing brain metastasis is a principal goal of cancer therapy, the cellular mechanisms and molecular regulators controlling the transmigration of cancer cells into the brain are still not clearly illustrated. We analyzed the mRNA expression profiles of metastatic brain tissues and TNF-α treated cancer cells to understand the changes in adhesion molecule expression during the tumor phase. To imitate the tumor microenvironment, an in vitro model was developed and the low or high metastatic potential lung tumor cells (A549 or H358) were cultured with the human brain microvascular endothelial cells (hBMECs) under TNF-α treatment. The analysis of online database indicated an altered expression for adhesion molecules and enrichment of their associated signaling pathways. TNF-α treatment activated hBMECs via up-regulating several adhesion molecules, including ICAM1, CD112, CD47, and JAM-C. Meanwhile, TNF-α induced an increased expression of adhesion molecule ligands such as ALCAM and CD6 in both A549 and H358. Moreover, the expression of adhesion molecules and the ligands were also increased both in A549- or H358-hBMECs mixed culture system, which promoted tumor cells adhesion to endothelial cells. These results suggested that the enhanced interaction between tumor cells and brain microvascular endothelium might facilitate the incidence of metastatic brain tumors and further offer a better comprehension of brain metastasis prevention and treatment.