title: P-Selectin-Mediated Adhesion between Platelets and Tumor Cells Promotes Intestinal Tumorigenesis in Apc(Min/+) Mice.
abstract: Studies have indicated that platelets play an important role in tumorigenesis, and an abundance of platelets accumulate in the ovarian tumor microenvironment outside the vasculature. However, whether cancer cells recruit platelets within intestinal tumors and how they signal adherent platelets to enter intestinal tumor tissues remain unknown. Here, we unexpectedly found that large numbers of platelets were deposited within human colorectal tumor specimens using immunohistochemical staining, and these platelets were fully associated with tumor development. We further report the robust adhesion of platelet aggregates to tumor cells within intestinal tumors, which occurs via a mechanism that is dependent on P-selectin (CD62P), a cell adhesion molecule that is abundantly expressed on activated platelets. Using spontaneous intestinal tumor mouse models, we determined that the genetic deletion of P-selectin suppressed intestinal tumor growth, which was rescued by the infusion of wild-type platelets but not P-selectin(-/-) platelets. Mechanistically, platelet adhesion to tumor cells induced the secretion of vascular endothelial growth factor (VEGF) to promote angiogenesis and accelerate intestinal tumor cell proliferation. Our results indicate that the adherence of platelets to tumor cells could promote tumor growth and metastasis. By targeting this platelet-tumor cell interaction, recombinant soluble P-selectin may have therapeutic value for the treatment of intestinal tumors.
authors.affiliation: 1. Department of Pathology, Guangzhou Medical University, Guangzhou, Guangdong 510182, China ; 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Qi
authors.affiliation: 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Simei
authors.initials: S
authors.lastname: Guo
authors.affiliation: 3. Department of Gastrointestinal Surgery and Department of Pathology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.affiliation: 3. Department of Gastrointestinal Surgery and Department of Pathology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Chunkui
authors.initials: C
authors.lastname: Shao
authors.affiliation: 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Li
authors.affiliation: 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Jiangchao
authors.initials: J
authors.lastname: Li
authors.affiliation: 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: He
authors.affiliation: 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1. Department of Pathology, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D017491:Genes, APC; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D007422:Intestines; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010973:Platelet Adhesiveness; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019007:P-Selectin; D042461:Vascular Endothelial Growth Factor A
keywords: P-selectin; VEGF; intestinal tumor; platelets