P-selectin-mediated platelet adhesion promotes tumor growth.

Cuiling Qi,Xiaodong He,Liu Cao,Tian Lan,Lijing Wang,Simei Guo,Jie Ye,Yang Yang,Jiangchao Li,Jialin Li,Jianguo Geng,Bin Li,Jia Zhou,Weijie Zhou,Qianqian Zhang,Bo Wei

doi:10.18632/oncotarget.3164

Abstract

Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.

Highlights

Platelets profoundly promote cell transformation, survival and growth by releasing several kinds of growth factors, such as platelet-derived growth factors (PDGFs), fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs) and epidermal growth factor (EGFs) [1, 2]
To test whether platelets infiltrate into solid tumors, we have examined platelet deposition in several types of human cancer specimens using immunofluorescent staining of βIIb for platelets, cytokeratin 8 (CK8) for tumor cells and DAPI for nuclear DNA
We have shown that platelets are actively infiltrated to solid tumors, such as insulinoma and malignant melanoma, through a P-selectin-dependent mechanism, where they secrete VEGF, and undoubtedly many other growth factors, thereby leading to angiogenesis and tumor growth

Summary

Introduction

Platelets profoundly promote cell transformation, survival and growth by releasing several kinds of growth factors, such as platelet-derived growth factors (PDGFs), fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs) and epidermal growth factor (EGFs) [1, 2]. Platelet-derived TGFβ induces an epithelial-mesenchymallike transition and promotes tumor metastasis [3]. Platelets can aggregate around tumor cells to protect them from clearance by immune-mediated pathways [4]. Overwhelming clinical and experimental evidence demonstrates that the depletion of platelets by a variety of mechanisms reduces tumor growth and metastasis [5,6,7], the therapeutic depletion of platelets is not clinically feasible due to the high risk of potentially fatal hemorrhage

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Results

Conclusion