Induction of cytokines and growth factors by rapamycin in the microenvironment of brain metastases of lung cancer

Kim,Se  Hoon; Lee,Jung  Eun; Yang,Seung-Ho; Lee,Sang  Won

doi:10.3892/ol.2013.1135

Induction of cytokines and growth factors by rapamycin in the microenvironment of brain metastases of lung cancer

Authors:
- Se Hoon Kim
- Jung Eun Lee
- Seung-Ho Yang
- Sang Won Lee
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Affiliations: Department of Pathology, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Republic of Korea, Department of Neurosurgery, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Kunggido 442-723, Republic of Korea
Published online on: January 15, 2013 https://doi.org/10.3892/ol.2013.1135
Pages: 953-958

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Abstract

The association between rapamycin and astrocytes in a tumor-bearing mouse model with brain metastases of non‑small cell lung cancer (NSCLC) was investigated. For in vitro experiments, NCI-H358, a human lung adenocarcinoma cell line, was co-cultured with immortalized astrocytes, and treated with rapamycin, an mTOR inhibitor. We evaluated the expression of interleukin-1 (IL-1), interleukin-3 (IL-3), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) in tumor cells in vivo. Rapamycin is cytotoxic in vitro; however, co-culturing tumor cells and astrocytes induced tumor cell survival. IL-1, IL-3, IL-6, TNF-α, TGF-β, PDGF, MCP-1 and MIP-1 expression were higher in rapamycin-treated mice compared to the control group, however, IGF-1 expression was lower. Notably, treatment with rapamycin before inoculating tumor cells affected cytokine expression in the tumor microenvironment. We suggest that growth factors and cytokines in the tumor microenvironment play a role in the survival of cancer cells in brain metastases.

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