The angiogenic responses induced by release of angiogenic proteins from tumor cell-activated platelets are regulated by distinct molecular pathways.
There is mounting evidence that tumor angiogenesis can be regulated by platelets (Plts), which serve as major sources and delivery vehicles of many proangiogenic cytokines including transforming growth factor-β and vascular endothelial growth factor. Although considerable progress has been made in understanding the role for Plt secretion in tumor angiogenesis, very little is known about the precise mechanisms underlying cancer cell induction of Plt granule release. Here, we demonstrated that nonsmall cell lung cancer (NSCLC) cells directly induced Plt secretion of several angiogenic regulatory cytokines that promoted angiogenesis in concert. Moreover, we discovered that these Plt-derived angiogenesis modulators were regulated by different molecular pathways and could be largely inhibited by combination of multiple signaling inhibitors. Our present studies indicated that manipulation of Plt secretion of angiogenic cytokines without compromising hemostatic functions could provide a novel option for management of tumor angiogenesis and metastasis in NSCLC patients with thrombocytosis.
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.|Department of Pharmacy, Yancheng Health Vocational and Technical College, Yancheng, China.
Hongyan
H
Wu
Department of Pharmacology, Hanlin College, Nanjing University of Chinese Medicine, Taizhou, China.
Fangtian
F
Fan
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Zhaoguo
Z
Liu
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Feng
F
Zhang
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Yuping
Y
Liu
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Zhonghong
Z
Wei
First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Cunsi
C
Shen
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Yuzhu
Y
Cao
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Aiyun
A
Wang
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Yin
Y
Lu
D001777:Blood Coagulation / Q000235:genetics; D001792:Blood Platelets / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic; D015539:Platelet Activation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013922:Thrombocytosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
COX-1; NSCLC; P2Y12; integrin αIIbβ3; platelet secretion; tumor angiogenesis