Abstract
Breast cancer brain metastasis has been recognized as one of the central issues in breast cancer research. The elucidation of the processes and pathways that mediate this step will provide important clues for a better understanding of breast cancer metastasis. Increasing evidence suggests that aberrant glycosylation patterns greatly contribute to cell invasion and cancer metastasis. Herein, we combined next-generation RNA sequencing with liquid chromatography-tandem mass spectrometry-based proteomic and N-glycomic analysis from five breast cancer cell lines and one brain cancer cell line to investigate the possible mechanisms of breast cancer brain metastasis. The genes/proteins associated with cell movement were highlighted in breast cancer brain metastasis. The integrin signaling pathway and the up-regulation of α-integrin (ITGA2, ITGA3) were associated with the brain metastatic process. 12 glycogenes showed unique expression in 231BR, which could result in an increase of sialylation during brain metastasis. In agreement with the changes of glycogenes, 60 out of 63 N-glycans that were identified exhibited differential expression among cell lines. The correlation between glycogenes and glycans revealed the importance of sialylation and sialylated glycans in breast cancer brain metastasis. Highly sialylated N-glycans, which were up-regulated in brain-seeking cell line 231BR, likely play a role in brain metastasis.
Highlights
The key event of breast cancer brain metastasis is the penetration of breast cancer cells through the blood-brain barrier[9]
MDA-MB-231BR (231BR) has a 100% trend to metastasize to the brain, and it cannot migrate to any other organs; the brain is not the first target for other cell lines, which can migrate to areas such as bone and lung6,32. 231BR is the subline of MDA-MB-231 (231). 231 was initially injected into a nude mouse, and tumor cells from its brain metastatic site were isolated and injected into another mouse
We investigated and correlated transcriptomics, proteomics, and glycomics of five breast cancer cell lines and one brain cancer cell line
Summary
The key event of breast cancer brain metastasis is the penetration of breast cancer cells through the blood-brain barrier[9]. In addition to protecting the brain, the blood-brain barrier can prevent drugs from entering the brain; brain metastasis treatments pose a great challenge. In recent years breast cancer brain metastasis has attracted much research interest, and many efforts have been made to elucidate the mechanisms of this process[6,7,12,13,14]. The Massague group found that the ST6GALNAC5 glycogene contributes to breast cancer brain metastasis by increasing the adhesion of breast cancer cells to the blood-brain barrier[5]. This is the only glycogene which is directly confirmed to be associated with breast cancer brain metastasis
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