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Int J Biol Sci 2016; 12(11):1289-1297. doi:10.7150/ijbs.16405

Research Paper

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.

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

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How to cite this article:
Qi C, Li J, Guo S, Li M, Li Y, Li J, Zhang Q, Zheng L, He X, Zheng X, He Y, Wang L, Wei B. P-selectin-mediated LOX expression promotes insulinoma growth in Rip1-Tag2 mice by increasing tissue stiffness. Int J Biol Sci 2016; 12(11):1289-1297. doi:10.7150/ijbs.16405. Available from http://www.ijbs.com/v12p1289.htm