TY - JOUR
T1 - Upregulation of phosphorylated sphingosine kinase 1 expression in colitis-associated cancer
AU - Yuza, Kizuki
AU - Nagahashi, Masayuki
AU - Shimada, Yoshifumi
AU - Nakano, Mae
AU - Tajima, Yosuke
AU - Kameyama, Hitoshi
AU - Nakajima, Masato
AU - Takabe, Kazuaki
AU - Wakai, Toshifumi
N1 - Funding Information:
The authors would like to acknowledge funding from the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research, Grant Numbers 17K10579 for K. Y., 15H05676 and 15K15471 for M. Nagahashi, 15K10130 for Y.S., 17K10663 for M. Nakano, 16K21041 for Y.T., 17K10624 for H.K., 17K10692 for M. Nakajima, and 15H04927 and 16K15610 for T.W.; M. Nagahashi is also supported by the Takeda Science Foundation and the Tsukada Medical Foundation. K.T. is supported by an NIH/NCI grant R01CA160688 and a Susan G. Komen Investigator Initiated Research Grant IIR12222224.
Publisher Copyright:
© 2018 Elsevier Inc.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/11
Y1 - 2018/11
N2 - Background: Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that is generated by sphingosine kinase 1 (SphK1) and is known to play an important role in inflammation and cancer progression. Moreover, SphK1 and S1P act as upstream mediators of proinflammatory cytokine interleukin 6 (IL-6) and signal transducer and activator of transcription-3 (STAT3). We hypothesized that the expression levels of phosphorylated SphK1 (pSphK1), phosphorylated STAT3 (pSTAT3), and IL-6 are universally higher in CAC patients than in sporadic colorectal cancer (CRC) patients because all of these factors are associated with inflammation. In this study, we determined the expression levels of pSphK1 in patients with sporadic CRC and CAC and clarified the importance of S1P in CAC patients. Materials and methods: We randomly selected 10 sporadic CRC patients and 10 CAC patients who underwent curative resection, and we examined their surgical specimens by immunohistochemistry. We determined the expression levels of pSphK1, pSTAT3, and IL-6 in these samples. Results: We found pSphK1 expression to be more prevalent in CAC patients (P = 0.019) and to have a higher immunohistochemistry score (P = 0.005) than in sporadic CRC patients. However, the expression of pSTAT3 and IL-6 did not differ between the patient groups. Conclusions: To our knowledge, this is the first report comparing pSphK1 expression levels in CAC with those in sporadic CRC. The high levels of pSphK1 expression in CAC suggest an important role of S1P in the disease process of CAC.
AB - Background: Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that is generated by sphingosine kinase 1 (SphK1) and is known to play an important role in inflammation and cancer progression. Moreover, SphK1 and S1P act as upstream mediators of proinflammatory cytokine interleukin 6 (IL-6) and signal transducer and activator of transcription-3 (STAT3). We hypothesized that the expression levels of phosphorylated SphK1 (pSphK1), phosphorylated STAT3 (pSTAT3), and IL-6 are universally higher in CAC patients than in sporadic colorectal cancer (CRC) patients because all of these factors are associated with inflammation. In this study, we determined the expression levels of pSphK1 in patients with sporadic CRC and CAC and clarified the importance of S1P in CAC patients. Materials and methods: We randomly selected 10 sporadic CRC patients and 10 CAC patients who underwent curative resection, and we examined their surgical specimens by immunohistochemistry. We determined the expression levels of pSphK1, pSTAT3, and IL-6 in these samples. Results: We found pSphK1 expression to be more prevalent in CAC patients (P = 0.019) and to have a higher immunohistochemistry score (P = 0.005) than in sporadic CRC patients. However, the expression of pSTAT3 and IL-6 did not differ between the patient groups. Conclusions: To our knowledge, this is the first report comparing pSphK1 expression levels in CAC with those in sporadic CRC. The high levels of pSphK1 expression in CAC suggest an important role of S1P in the disease process of CAC.
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U2 - 10.1016/j.jss.2018.05.085
DO - 10.1016/j.jss.2018.05.085
M3 - Article
C2 - 30278948
AN - SCOPUS:85049075428
VL - 231
SP - 323
EP - 330
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
ER -