Int J Biol Sci 2015; 11(6):679-687. doi:10.7150/ijbs.11589
P-Selectin-Mediated Adhesion between Platelets and Tumor Cells Promotes Intestinal Tumorigenesis in ApcMin/+ Mice
1. Department of Pathology, Guangzhou Medical University, Guangzhou, Guangdong 510182, China
2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China
3. Department of Gastrointestinal Surgery and Department of Pathology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China
* These authors contributed equally to this work.
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.
Keywords: P-selectin, platelets, intestinal tumor, VEGF
Qi C, Li B, Guo S, Wei B, Shao C, Li J, Yang Y, Zhang Q, Li J, He X, Wang L, Zhang Y. P-Selectin-Mediated Adhesion between Platelets and Tumor Cells Promotes Intestinal Tumorigenesis in ApcMin/+ Mice. Int J Biol Sci 2015; 11(6):679-687. doi:10.7150/ijbs.11589. Available from http://www.ijbs.com/v11p0679.htm