title: P-selectin-mediated LOX expression promotes insulinoma growth in Rip1-Tag2 mice by increasing tissue stiffness.
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.
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Qi
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Li
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Simei
authors.initials: S
authors.lastname: Guo
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Mengshi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology, University of Guangzhou Chinese Medicine, Guangzhou, Guangdong 510000, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Jiangchao
authors.initials: J
authors.lastname: Li
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Gastrointestinal Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Pathology, University of Guangzhou Chinese Medicine, Guangzhou, Guangdong 510000, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: He
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
mesh_terms: D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D003094:Collagen / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D019007:P-Selectin; C490620:Ralbp1 protein, mouse; D000629:Aminopropionitrile; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase; D006909:Hydroxyproline
keywords: LOX; P-selectin; Rip1-Tag2 mice; insulinoma; tissue stiffness