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dc.contributor.authorKaur, A-
dc.contributor.authorRiaz, S-
dc.contributor.authorSingh, S-
dc.contributor.authorKishore, U-
dc.identifier.citationKaur, A., Riaz, M.S., Singh, S.K. and Kishore, U. (2018) 'Human Surfactant Protein D Suppresses Epithelial-to-Mesenchymal Transition in Pancreatic Cancer Cells by Downregulating TGF-β', Frontiers in Immunology, 9, 1844, pp. 1-13. doi: 10.3389/fimmu.2018.01844.en_US
dc.description.abstractCopyright: © 2018 Kaur, Riaz, Singh and Kishore. Human surfactant protein-D (SP-D), an innate immune pattern recognition soluble factor, is known to modulate a range of cytokines and chemokines, such as TNF-α and TGF-β at mucosal surfaces during infection, allergy, and inflammation. A recent study has shown that treatment with a recombinant fragment of human SP-D (rfhSP-D) for 48 h induces apoptosis in pancreatic cancer cells. Our hypothesis is that at earlier time points, SP-D can also influence key cytokines as a part of its putative role in the immune surveillance against pancreatic cancer, where the inflammatory tumor microenvironment contributes to the epithelial-to-mesenchymal transition (EMT), invasion, and metastasis. Here, we provide the first evidence that rfhSP-D can suppress the invasive-mesenchymal properties of highly aggressive pancreatic cancer cells. Mechanistically, rfhSP-D inhibited TGF-β expression in a range of pancreatic cancer cell lines, Panc-1, MiaPaCa-2, and Capan-2, thereby reducing their invasive potential. Smad2/3 expression diminished in the cytoplasm of rfhSP-D-treated cells as compared to the untreated control, suggesting that an interrupted signal transduction negatively affected the transcription of key mesenchymal genes. Thus, expressions of Vimentin, Zeb1, and Snail were found to be downregulated upon rfhSP-D treatment in the pancreatic cancer cell lines. Furthermore, blocking TGF-β with neutralizing antibody showed similar downregulation of mesenchymal markers as seen with rfhSP-D treatment. This study highlights yet another novel innate immune surveillance role of SP-D where it interferes with EMT induction by attenuating TGF-β pathway in pancreatic cancer.en_US
dc.description.sponsorshipMax-Elder Research Granten_US
dc.format.extent1 - 13-
dc.publisherFrontiers Mediaen_US
dc.rightsCopyright: © 2018 Kaur, Riaz, Singh and Kishore. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.-
dc.subjectsurfactant proteinen_US
dc.subjectsurfactant protein-Den_US
dc.subjectpancreatic canceren_US
dc.subjectepithelial-to-mesenchymal transitionen_US
dc.subjecttransformation growth factoren_US
dc.titleHuman Surfactant Protein D suppresses epithelial-to-mesenchymal transition in pancreatic cancer cells by downregulating TGF-βen_US
dc.relation.isPartOfFrontiers in Immunology-
Appears in Collections:Dept of Life Sciences Research Papers

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