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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 321 - 332 (12page)
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The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-β (TGF-β)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.
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참고문헌 (35)
참고문헌 신청
Balkwill, F. / 2001 / Inflammation and cancer:back to Virchow? / Lancet 357:539~545
Bao, L. / 2016 / Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma / Tumour Biol 37:15043~15052
Bardeesy, N. / 2006 / Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer / Genes Dev 20:3130~3146
Budczies, J. / 2015 / The landscape of metastatic progression patterns across major human cancers / Oncotarget 6:570~583
Cheng, H. / 2015 / Decreased SMAD4 expression is associated with induction of epithelial-to-mesenchymal transition and cetuximab resistance in head and neck squamous cell carcinoma / Cancer Biol. Ther 16:1252~1258
Bao, L. / 2016 / Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma / Tumour Biol 37:15043~15052
Bardeesy, N. / 2006 / Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer / Genes Dev 20:3130~3146
Budczies, J. / 2015 / The landscape of metastatic progression patterns across major human cancers / Oncotarget 6:570~583
Cheng, H. / 2015 / Decreased SMAD4 expression is associated with induction of epithelial-to-mesenchymal transition and cetuximab resistance in head and neck squamous cell carcinoma / Cancer Biol. Ther 16:1252~1258
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