國家衛生研究院 NHRI:Item 3990099045/11676
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    题名: Lung tumorigenesis alters the expression of Slit2-exon15 splicing variants in tumor microenvironment
    作者: Wu, MF;Chuang, CY;Lin, P;Chen, WT;Su, SE;Liao, CY;Jan, MS;Chang, JT
    贡献者: National Institute of Environmental Health Sciences
    摘要: Slit2 expression is downregulated in various cancers, including lung cancer. We identified two Slit2 splicing variants at exon15-Slit2-WT and Slit2-DeltaE15. In the RT-PCR analyses, the Slit2-WT isoform was predominantly expressed in all the lung cancer specimens and in their normal lung counterparts, whereas Slit2-DeltaE15 was equivalently or predominantly expressed in 41% of the pneumothorax specimens. A kRas(G12D) transgenic mice system was used to study the effects of tumorigenesis on the expressions of the Slit2-exon15 isoforms. The results revealed that a kRas(G12D)-induced lung tumor increased the Slit2-WT/Slit2-DeltaE15 ratio and total Slit2 expression level. However, the lung tumors generated via a tail vein injection of lung cancer cells decreased the Slit2-WT/Slit2-DeltaE15 ratio and total Slit2 expression level. Interestingly, the lipopolysaccharide (LPS)-induced lung inflammation also decreased the Slit2-WT/Slit2-DeltaE15 ratio. Since Slit2 functions as an anti-inflammatory factor, the expression of Slit2 increases in kRas(G12D) lungs, which indicates that Slit2 suppresses immunity during tumorigenesis. However, an injection of lung cancer cells via the tail vein and the LPS-induced lung inflammation both decreased the Slit2 expression. The increased Slit2 in the tumor microenvironment was mostly Slit2-WT, which lacks growth inhibitory activity. Thus, the results of our study suggested that the upregulation of Slit2-WT, but not Slit2-DeltaE15, in a cancer microenvironment is an important factor in suppressing immunity while not interfering with cancer growth.
    日期: 2019-02-01
    關聯: Cancers. 2019 Feb 1;11(2):Article number 166.
    Link to: http://dx.doi.org/10.3390/cancers11020166
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2072-6694&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000460747200040
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85062430903
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