CCL21/CCR7 axis in regulating glioblastoma stem cell-lymphatic endothelial cell interaction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA901970 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14850747_1.fastq.gz | Fastqsanger.gz | |||
| SRR14850747_2.fastq.gz | Fastqsanger.gz | |||
| SRR14850748_1.fastq.gz | Fastqsanger.gz | |||
| SRR14850748_2.fastq.gz | Fastqsanger.gz | |||
| SRR14850749_1.fastq.gz | Fastqsanger.gz |
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2011-05-19 | E-GEOD-26229 | biostudies-arrayexpress
Project description:Chemokines and adhesion molecules upregulated in lymphatic endothelial cells (LECs) during tissue inflammation are believed to enhance dendritic cell (DC) migration to draining lymph nodes (dLNs), but the in vivo control of this process is not well understood. By performing transcriptional profiling of LECs isolated from murine skin, we found that inflammation induced by a contact hypersensitivity (CHS) response upregulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines in LECs. Furthermore, lymphatic lineage markers like Prox-1, VEGFR3 and LYVE-1 were significantly downregulated during CHS. By contrast, skin inflammation induced by Complete Freund’s adjuvant (CFA) induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. In FITC painting experiments, DC migration to dLNs was more strongly increased in CFA- as compared to CHS-induced inflammation. Interestingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 in LECs. However, the requirement for CCR7 signaling became further pronounced during inflammation, whereas CCR7-independent signals only had a minor role in enhancing DC migration. Collectively, these findings indicate that inflammation-induced DC migration is stimulus-dependent and only moderately enhanced by LEC-induced genes other than CCL21.
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Project description:The lymphatic system is a major gateway for tumor cell dissemination but the mechanisms of how tumor cells gain access to lymphatic vessels are not completely understood. Breast cancer cells undergoing epithelial-mesenchymal transition (EMT) gain invasive and migratory properties. Overexpression of the cytokine transforming growth factor β1 (TGF-b1), a potent inducer of EMT, is frequently detected in the tumor microenvironment and correlates with invasion and lymph metastasis. Recently, we reported that TGF-b1 stimulated breast cancer cells with EMT properties migrate in a targeted fashion towards the lymphatic system via CCR7/CCL21-mediated chemotaxis, similar to dendritic cells during inflammation. Here, we aimed to identify additional chemotactic factors and receptors that could be involved in this. Through a combination of RNA sequencing analysis, database screening and invasion assays we identified IL-7/IL7R and IL-15/IL15R as pairs of chemokines and chemokine receptors with potential roles in promoting chemotactic migration of breast cancer cells with EMT properties towards the lymphatics. The results warrant studies to further explore their possible roles in lymph metastasis in breast cancer. Moreover, they demonstrate the capacity of TGF-b1 to orchestrate crosstalk between tumor cells and lymphatic endothelial cells.
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