EFFECT OF ANTI-TSLPR MONOCLONAL ANTIBODY ON VIABILITY, PROAPOPTOTIC GENES EXPRESSION, AND PRODUCTION OF PRO-INFLAMMATORY CYTOKINES IN MCF-7 AND A549 CELLS
DOI:
https://doi.org/10.15407/exp-oncology.2023.02.211Keywords:
TSLP, breast cancer, lung cancer, viability, inflammation, apoptosisAbstract
Background. Thymic stromal lymphopoietin (TSLP) and its receptor (TSLPR) are expressed in various cancer cells. However, their role in cancer development is not well defined. Aim. To investigate the effects of anti-TSLPR antibody on the viability, proapoptotic genes expression, and production of pro-inflammatory cytokines in MCF-7 and A549 cancer cells. Materials and Methods. MCF-7 and A549 cells were exposed to anti-TSLPR monoclonal antibody for 24, 48, and 72 h. The effect on cell viability was examined by MTT assay. The expression levels of TP53, BAX, and CASP3 genes were evaluated by the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Levels of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and transforming growth factor (TGF-β1) were measured by the enzyme-linked immunosorbent assay (ELISA). Results. The treatment of MCF-7 cells with anti- TSLPR antibody slightly stimulates cell proliferation after 48 h and 72 h following initial cytotoxicity in 24 h with a significant reduction in IL-6 and TNF-α production. A significant increase in the BAX expression in anti-TSLPR treated cells at a concentration of 2.5 μg/ml at 24-h point was evident. In anti-TSLPR-treated A549 cells, no decrease in cell count was observed, and slight dose-dependent stimulation of cell proliferation was evident in 48 h and 72 h of culture. A significant increase in TP53, BAX, and CASP3 expression upon treatment with 2.5 μg/ml of anti-TSLPR was evident in A549 cells. Conclusion. The effects of anti-TSLPR on cell viability, proapoptotic gene expression, and production of pro-inflammatory cytokines (IL-6 and TNF-α) vary in MCF-7 and A549 cells.
References
Sebastian K, Borowski A, Kuepper M, et al. Signal transduction around thymic stromal lymphopoietin (TSLP) in atopic asthma. Cell Commun Signal. 2008;6:4-11. doi: 10.1186/1478-811X-6-5
Xie F, Meng YH, Liu LB, et al. Cervical carcinoma cells stimulate the angiogenesis through TSLP promoting growth and activation of vascular endothelial cells. Am J Reprod Immunol. 2013;70:69-79. doi: 10.1111/aji.12104
Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116. doi: 10.1172/JCI89820.
Corren J, Ziegler SF. TSLP : from allergy to cancer. Nat Immunol. 2019;20:1603-1609. doi: 10.1038/s41590-019- 0524-9.
Pedroza-Gonzalez A, Xu K, Wu TC, et al. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J Exp Med. 2011;208:479-490. doi: 10.1084/jem.20102131.
Zhao H, Li H, Yu J, et al. The expression of TSLP and its relationship with the number of infiltrating regulatory T cells in lung cancer. Chin J Clin Oncol. 2010;37:126-130.
Xie F, Liu LB, Shang WQ, et al. The infiltration and functional regulation of eosinophils induced by TSLP pro- mote the proliferation of cervical cancer cell. Cancer Lett. 2015;364:106-117. doi: 10.1016/j.canlet.2015.04.029
Watanabe J, Saito H Miyatani K, et al. TSLP expression and high serum TSLP level indicate a poor prognosis in gastric cancer patients. Yonago Acta Med. 2015;58:137-143. PMID: 26538800; PMCID: PMC4626360.
Stoian C, Mambo N G, McCarthy P, et al. Targeting TSLP-induce upregulation of Mcl-1 for the treatment of Ph- like ALL with CRLF2 alterations [abstract]. In: Proc. Am. Assoc. Cancer Res Annual Meeting; Washington, DC. Philadelphia (PA): AACR; Cancer Res. 2017; 77:Abstract nr 5829. doi: 10.1158/1538-7445.AM2017-5829
Yue W, Lin Y, Yang X, et al.Thymic stromal lymphopoietin (TSLP) inhibits human colon tumor growth by promo- ting apoptosis of tumor cells. Oncotarget. 2016;7:16840. doi: 10.18632/oncotarget.7614
Demehri S, Cunningham TJ, Manivasagam S, et al. Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis. J Clin Invest. 2016;126:1458-1470. doi: 10.1172/JCI83724
O’Shea JJ, Gadina M, Siegel RM. Cytokines and Cytokine Receptors. In Clinical Immunology, Fifth Edition. Else- vier, 2019: 127-155. doi: 10.1016/B978-0-7020-6896-6.00009-0
Miazgowicz MM, Elliott MS, Debley JS, et al. Respiratory syncytial virus induces functional thymic stromal lym- phopoietin receptor in airway epithelial cells. J Inflam Res. 2013;6:53-61. doi: 10.2147/JIR.S42381
Kuan EL, Ziegler SF. A tumor-myeloid cell axis, mediated via the cytokines IL-1α and TSLP, promotes the prog- ression of breast cancer. Nat Immunol. 2018;19:366-374. doi: 10.1038/s41590-018-0066-6
Li H, Zhao H, Yu J, et al. Increased prevalence of regulatory T cells in the lung cancer microenvironment: A role of thymic stromal lymphopoietin. Cancer Immunol Immunother. 2011;60:1587-1596. doi: 10.1007/s00262-011- 1059-6
Goswami I, Coutermarsh-Ott S, Morrison RG, et al. Irreversible electroporation inhibits pro-cancer inflamma- tory signaling in triple-negative breast cancer cells. Bioelectrochemistry. 2017;113:42-50.doi: 10.1016/j. bioelec- hem.2016.09.003
Olkhanud PB, Rochman Y, Bodogai M, et al. Thymic stromal lymphopoietin is a key mediator of breast cancer progression. J Immunol. 2011;186:5656-5662. doi: 10.4049/jimmunol.1100463
Semlali A, Almutairi M, Parine NR, et al. Expression and allele frequencies of thymic stromal lymphopoietin are a key factor of breast cancer risk. Genetics Genomics. 2019;7:e813. doi: 10.1002/mgg3.813
Shi H, Zhao L, Guo X, et al. Arctigenin attenuates breast cancer progression through decreasing GM-CSF/TSLP/ STAT3/β-catenin signaling. Int J Mol Sci. 2020; 21:6357 doi:10.3390/ijms21228850
Ghirelli C, Sadacca B, Reyal F, Zollinger R, et al. No evidence for TSLP pathway activity in human breast cancer.
Oncoimmunology. 2016;5:e1178438. doi:10.1080/2162402X.2016.1178438
Zhu T, Zheng J, Hu S, et al. Construction and validation of an immunity-related prognostic signature for breast cancer. Aging (Albany NY). 2020;12:21597-21612. doi:10.18632/aging.103952
Cavic M, Jokic V, Marinkovic M, et al. The value of Th2-related thymic stromal lymphopoietin as a prognostic and predictive biomarker in non-small cell lung cancer. J Thorac Oncol. 2021;16:S705–S706. doi: 10.1016/S1556- 0864(21)01859-1
Lau S, Wong S, Wang B, et al. Early expansion of M-MDSCs and high plasma TSLP levels as predictors of pri- mary resistance to PD1 inhibitors in metastatic NSCLC. J Thorac Oncol. 2021;16:S332–S333. doi: 10.1016/j. jtho.2021.01.515
Talaat RM, Abo-zeid TM, Abo-elfadl MT, et al. Combined hyperthermia and radiation therapy for treatment of hepatocellular carcinoma. Asian Pac J Cancer Prev. 2019;20:2303-2310. doi:10.31557/APJCP.2019.20.8.2303
El-Maadawy EA, Elshal MF, Bakry RM, et al. Regulation of CD4+ CD25+ FOXP3+ cells in pediatric acute lym- phoblastic leukemia (ALL): Implication of cytokines and miRNAs. Mol Immunol. 2020;124:1-8. doi: 10.1016/j. molimm.2020.05.002
Talaat RM, Mohamed SF, Bassyouni IH, et al. Cytokine Th1 / Th2 / Th17 / Treg cytokine imbalance in systemic lu- pus erythematosus ( SLE ) patients : Correlation with disease activity. Cytokine. 2015;72:146-153. doi: 10.1016/j. cyto.2014.12.027
Yu H, Yang J, Li Y, et al. The expression of thymic stromal lymphopoietin in primary tumors of breast cancer is as- sociated with prognosis. Chin J Cell Mol Immunol. 2015;31:239-243. PMID: 25652868
Hartgring SAY, Willis CR, Dean CE, et al. Critical proinflammatory role of thymic stromal lymphopoietin and its receptor in experimental autoimmune arthritis. Arthritis Rheumatism. 2011;63:1878-1887. doi: 10.1002/ art.30336
Yoou M, Nam S, Hyun M, et al. Ameliorative effect of atractylenolide III in the mast cell proliferation induced by TSLP. Food Chem Toxicol. 2017;106:78-85. doi: 10.1016/j.fct.2017.05.042
Shan L, Redhu NS, Saleh A, et al.Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemo- kines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2 p38, and JNK) and STAT3 pathways. J Immunol. 2010;184:7134-7143. doi: 10.4049/jimmunol.0902515.
Ito T, Wang Y, Duramad O, et al. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell res- ponse through the OX40 ligand. J Exp Med. 2005;202(9):1213-1223. doi: 10.1084/jem.20051135.
Burkard-Mandel L, Neill RO, Colligan S, et al. Tumor-derived thymic stromal lymphopoietin enhances lung metastasis through an alveolar macrophage-dependent mechanism. Oncoimmunology. 2018;7(5):e1419115. doi: 10.1080/2162402X.2017.1419115.
Submitted: January 15, 2023
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.