The angiogenic responses induced by release of angiogenic proteins from tumor cell-activated platelets are regulated by distinct molecular pathways.

Abstract

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.

• Authors: Hongyan Wu, Fangtian Fan, Zhaoguo Liu, Feng Zhang, Yuping Liu, Zhonghong Wei, Cunsi Shen, Yuzhu Cao, Aiyun Wang, Yin Lu
• Journal: IUBMB life (IUBMB Life) Vol. 67 Issue 8 Pg. 626-33 (Aug 2015) ISSN: 1521-6551 [Electronic] England
• PMID: 26283102 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 International Union of Biochemistry and Molecular Biology.

Chemical References

• Cytokines
• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Blood Coagulation (genetics)
• Blood Platelets (metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Cytokines (metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Neovascularization, Pathologic
• Platelet Activation (genetics)
• Signal Transduction (genetics)
• Thrombocytosis (genetics, metabolism, pathology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)