LEC-induced gene expression changes in melanoma cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE100269 | GEO | 2018/05/01
REPOSITORIES: GEO
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Project description:Transcriptional profiling of melanoma-associated lymphatic endothelial cells (LECs)
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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 FreundM-bM-^@M-^Ys 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. Mouse ear skin single-cell suspensions were prepared by a fast protocol that minimizes the RNA degradation. Fluorescence-activated cell sorting (FACS) was used to sort lymphatic endothelial cells (LEC) from CHS inflammed and control skin. 4 pairs (each with one control and one CHS inflammed sample, sorted and extracted on the same day) of LECs were chosen based on the quality of extracted and amplified material. This gave 8 samples to analyze (4 biological replicates in each condition). Each sample was sorted from 3 mice.
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