Next Article in Journal
Novel CD37, Humanized CD37 and Bi-Specific Humanized CD37-CD19 CAR-T Cells Specifically Target Lymphoma
Previous Article in Journal
Optimization of the Clinical Setting Using Numerical Simulations of the Electromagnetic Field in an Obese Patient Model for Deep Regional Hyperthermia of an 8 MHz Radiofrequency Capacitively Coupled Device in the Pelvis
Article

Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth

1
Department of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
2
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 510006, China
3
Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
4
School of Medicine, Faculty of Medicine and Health Sciences, Keele University, Newcastle-under-Lyme ST5 5BG, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Andrea Morandi
Cancers 2021, 13(5), 980; https://doi.org/10.3390/cancers13050980
Received: 23 December 2020 / Revised: 17 February 2021 / Accepted: 19 February 2021 / Published: 26 February 2021
(This article belongs to the Section Molecular Cancer Biology)
Cytokines are a group of small proteins in the body that play an important part in boosting the immune system. Thymic stromal lymphopoietin (TSLP) is a cytokine that plays an important role in the maturation of T cells. Two variants of TSLP, long-form (lfTSLP) and short-form (sfTSLP), have been found, however their roles in cancers are not known. In this study, we discovered that sfTSLP, but not lfTSLP, is predominantly expressed in ovarian and endometrial cancers. The switch that turns the sfTSLP gene on or off is controlled by external modifications of DNA. Our results also found that sfTSLP promotes tumour growth through activating several signal pathways in cancer cells.
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. View Full-Text
Keywords: TSLP; short isoform; ovarian cancer; endometrial cancer; epigenetic regulation; tumour promotion TSLP; short isoform; ovarian cancer; endometrial cancer; epigenetic regulation; tumour promotion
Show Figures

Figure 1

MDPI and ACS Style

Chan, L.K.Y.; Lau, T.S.; Chung, K.Y.; Tam, C.; Cheung, T.H.; Yim, S.F.; Lee, J.H.S.; Leung, R.W.T.; Qin, J.; Or, Y.Y.Y.; Lo, K.W.; Kwong, J. Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth. Cancers 2021, 13, 980. https://doi.org/10.3390/cancers13050980

AMA Style

Chan LKY, Lau TS, Chung KY, Tam C, Cheung TH, Yim SF, Lee JHS, Leung RWT, Qin J, Or YYY, Lo KW, Kwong J. Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth. Cancers. 2021; 13(5):980. https://doi.org/10.3390/cancers13050980

Chicago/Turabian Style

Chan, Loucia K.Y., Tat S. Lau, Kit Y. Chung, Chit Tam, Tak H. Cheung, So F. Yim, Jacqueline H.S. Lee, Ricky W.T. Leung, Jing Qin, Yvonne Y.Y. Or, Kwok W. Lo, and Joseph Kwong. 2021. "Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth" Cancers 13, no. 5: 980. https://doi.org/10.3390/cancers13050980

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop