Pericytes Suppress Brain Metastasis from Lung Cancer In Vitro

Fujimoto, Fujimoto and Nakagawa, Shinsuke and Morofuji, Yoichi and Watanabe, Daisuke and Ujifuku, Kenta and Horie, Nobutaka and Izumo, Tsuyoshi and Niwa, Masami and Banks, William A. and Deli, Mária Anna and Matsuo, Takayuki (2019) Pericytes Suppress Brain Metastasis from Lung Cancer In Vitro. Cellular and Molecular Neurobiology, AiP. ISSN 0272-4340 (print), 1573-6830 (online)

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Abstract

Metastasis of lung cancer to the brain is associated with poor outcomes and limited therapeutic options. The blood-brain barrier (BBB) plays a major role in brain metastasis. However, little is known about the role of pericytes in brain metastasis formation. This study aimed to reveal the interaction between pericytes and cancer cells. We established in vitro BBB models with rat primary cultured BBB-related cells (endothelial cells, astrocytes, and pericytes) and investigated the relationship between BBB-related cells and metastatic cancer cell lines. We observed a significant decrease in transendothelial electrical resistance with metastatic cancer cells in monolayer and coculture models with astrocytes. In contrast, the coculture model with pericytes showed inhibition of the decrease in transendothelial electrical resistance with metastatic cancer cells. In addition, the expression of tight junction protein was preserved only in the coculture model with pericytes. The conditioned medium of pericytes with metastatic cancer cells suppressed the proliferation of the cancer cells significantly. This study revealed that brain pericytes are the major regulators of the resistance of the BBB to lung cancer metastasis to the brain. Pericytes exert an anti-metastatic effect and thus have potential for the preventive treatment of brain metastasis.

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