Differential reactions of microglia to brain metastasis of lung cancer

Bei Ping He, Jian Jun Wang, Xian Zhang, Yan Wu, Miao Wang, Boon Huat Bay, Alex Y Chang

Research output: Contribution to journalArticle

Abstract

The brain is a common metastatic site for various types of cancers, especially lung cancer. Patients with brain metastases have a poor prognosis in spite of radiotherapy and/or chemotherapy. It is postulated that immune cells in the brain may play a major role in cancer metastasis, dormancy, and relapse. Although microglia may serve as a major component in the brain immune system, the interaction between metastatic cancer cells and microglia is still largely unknown and remains to be elucidated. In this study, we have investigated microglial reactions in brain tissues with metastatic lung cancer cells and evaluated the cytotoxic effects of lipopolysaccharide (LPS)-activated microglia on metastatic lung cancer cells in vitro. In the vicinity of metastatic lung cancer mass in the brain, microglia showed signs of significant activation. There was an obvious increase in the number of microglia labeled with ionized calcium binding adaptor molecule 1 (lba-1) antibody, a specific marker of microglia. The microglia were observed to form a clear boundary between the tumor mass and normal brain tissue. In the region where the tumor mass was situated, only a few microglia expressed inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α), indicating differential activation in those microglia. The supernatant from LPS-activated microglia induced apoptosis of metastatic lung cancer cells in vitro in a dose- and time-dependent manner. However, at lower concentrations of activated microglial supernatant, trophic effects on cancer cells were observed, some lung cancer cells being insensitive to microglial cytotoxicity. Together with the observation that TNF-α alone induced proliferation of the tumor cells, the findings provide possible clues to the mechanism involved in metastasis of lung cancer cells to the brain.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalMolecular Medicine
Volume12
Issue number7-8
DOIs
StatePublished - Jul 2006
Externally publishedYes

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Microglia
Lung Neoplasms
Neoplasm Metastasis
Brain
Neoplasms
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Nitric Oxide Synthase Type II
Immune System
Radiotherapy
Cell Proliferation
Apoptosis
Calcium
Recurrence
Drug Therapy
Antibodies

ASJC Scopus subject areas

  • Genetics

Cite this

He, B. P., Wang, J. J., Zhang, X., Wu, Y., Wang, M., Bay, B. H., & Chang, A. Y. (2006). Differential reactions of microglia to brain metastasis of lung cancer. Molecular Medicine, 12(7-8), 161-170. https://doi.org/10.2119/2006-00033.He

Differential reactions of microglia to brain metastasis of lung cancer. / He, Bei Ping; Wang, Jian Jun; Zhang, Xian; Wu, Yan; Wang, Miao; Bay, Boon Huat; Chang, Alex Y.

In: Molecular Medicine, Vol. 12, No. 7-8, 07.2006, p. 161-170.

Research output: Contribution to journalArticle

He, BP, Wang, JJ, Zhang, X, Wu, Y, Wang, M, Bay, BH & Chang, AY 2006, 'Differential reactions of microglia to brain metastasis of lung cancer', Molecular Medicine, vol. 12, no. 7-8, pp. 161-170. https://doi.org/10.2119/2006-00033.He
He, Bei Ping ; Wang, Jian Jun ; Zhang, Xian ; Wu, Yan ; Wang, Miao ; Bay, Boon Huat ; Chang, Alex Y. / Differential reactions of microglia to brain metastasis of lung cancer. In: Molecular Medicine. 2006 ; Vol. 12, No. 7-8. pp. 161-170.
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