Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived
cytokine belonging to the
IL-7 family and a key initiator of allergic
inflammation. Two main
isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s) in
cancers are not yet clear.
mRNA expression was examined by
isoform-specific RT-PCR and
RNA in situ hybridisation. Epigenetic regulation was investigated by
chromatin immunoprecipitation-PCR and
bisulfite sequencing. Tumour progression was investigated by gene overexpression, cell viability assay,
cancer organoid culture and transwell invasion. Signals were investigated by
proteome profiler
protein array and
RNA-sequencing. With the use of
isoform-specific primers and probes, we uncovered that only sfTSLP was expressed in the cell lines and tumour tissues of human ovarian and
endometrial cancers. We also showed the epigenetic regulation of sfTSLP: sfTSLP transcription was regulated by
histone acetylation at promoters in
ovarian cancer cells, whereas silencing of the sfTSLP transcripts was regulated by promoter DNA methylation in
endometrial cancer cells. In vitro study showed that ectopically overexpressing sfTSLP promoted tumour growth but not invasion. Human phosphokinase array application demonstrated that the sfTSLP overexpression activated phosphorylation of multiple intracellular
kinases (including GSK3α/β, AMPKα1, p53, AKT1/2, ERK1/2 and Src) in
ovarian cancer cells in a context-dependent manner. We further investigated the impact of sfTSLP overexpression on transcriptome by
RNA-sequencing and found that EFNB2 and PBX1 were downregulated in ovarian and
endometrial cancer cells, suggesting their role in sfTSLP-mediated tumour growth. In conclusion, sfTSLP is predominantly expressed in ovarian and
endometrial cancers and promotes tumour growth.