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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2016 > Volume 12 Number 11 > Cuiling Qi1,*, Jialin Li1,*, Simei Guo1, Mengshi Li1, Yuanyuan Li3, Jiangchao Li1, Qianqian Zhang1, Lingyun Zheng1, Xiaodong He1, Xiaoming Zheng2, Yanli He3, Lijing Wang1,, Bo Wei2,

P-selectin-mediated LOX expression promotes insulinoma growth in Rip1-Tag2 mice by increasing tissue stiffness

Cuiling Qi1,*, Jialin Li1,*, Simei Guo1, Mengshi Li1, Yuanyuan Li3, Jiangchao Li1, Qianqian Zhang1, Lingyun Zheng1, Xiaodong He1, Xiaoming Zheng2, Yanli He3, Lijing Wang1,, Bo Wei2,
1. Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China 2. Department of Gastrointestinal Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China 3. Department of Pathology, University of Guangzhou Chinese Medicine, Guangzhou, Guangdong 510000, China * These authors contributed equally to this work.  Corresponding authors: Bo Wei or Lijing Wang. Address: Department of Gastrointestinal Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China, or Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China; Tel: +86-13527794069; E-mail: sanpi2013@163.com or wanglijing62@163.com
Abstract :

P-selectin, a cell adhesion molecule, is an important member of the selectin family. Recent studies have shown that P-selectin deletion inhibits tumor growth in Rip1-Tag2 mice by suppressing platelet accumulation in tumor tissues. This study aimed to evaluate whether and how P-selectin affects tumor stiffness in Rip1-Tag2 mice. To explore the role of P-selectin in tissue stiffness, we demonstrated that tumor progression in Rip1-Tag2 mice was correlated with tissue stiffness using immunofluorescence and histological staining. Furthermore, we showed that P-selectin deficiency significantly decreased tissue stiffness by inhibiting lysyl oxidase (LOX) expression. Our experiments involving Rip1-Tag2 mice treated with the LOX inhibitor BAPN showed that BAPN significantly abolished collagen deposition to decrease tumor stiffness and thus inhibit tumor growth. These results indicate that P-selectin deletion significantly decreases tumor stiffness in Rip1-Tag2 mice by inhibiting LOX expression. Further study demonstrated that P-selectin-mediated platelet accumulation increases tissue stiffness mainly by increasing LOX expression and thus promotes tumor growth. Therefore, P-selectin may be an effective therapeutic targeting for treating human insulinomas.

Keywords :
P-selectin, insulinoma, tissue stiffness, LOX, Rip1-Tag2 mice

Date Deposited : 07 Nov 2016 20:57

Last Modified : 07 Nov 2016 20:57

Official URL: http://www.ijbs.com/v12i11

Volume 12, Number 11, October 2016

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