Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899316 | Cancer Letters | 2016 | 11 Pages |
Abstract
Cancer stem cells (CSCs) are well known for their self-regeneration and tumorigenesis potential. In addition, the multi-differentiation potential of CSCs has become a popular issue and continues to attract increased research attention. Recent studies demonstrated that CSCs are able to differentiate into functional endothelial cells and participate in tumor angiogenesis. In this study, we found that ovarian cancer stem-like cells (CSLCs) activate the NF-κB and STAT3 signal pathways through autocrine CCL5 signaling and mediate their own differentiation into endothelial cells (ECs). Our data demonstrate that CSLCs differentiate into ECs morphologically and functionally. Anti-CCL5 antibodies and CCL5-shRNA lead to markedly inhibit EC differentiation and the tube formation of CSLCs, both in vitro and in vivo. Recombinant human-CCL5 significantly promotes ovarian CSLCs that differentiate into ECs and form microtube network. The CCL5-mediated EC differentiation of CSLCs depends on binding to receptors, such as CCR1, CCR3, and CCR5. The results demonstrated that CCL5-CCR1/CCR3/CCR5 activates the NF-κB and STAT3 signal pathways, subsequently mediating the differentiation of CSLCs into ECs. Therefore, this study was conducted based on the theory that CSCs improve tumor angiogenesis and provides a novel strategy for anti-angiogenesis in ovarian cancer.
Keywords
STAT3NF-κBCcl5EPCsCSCsHUVECSECsAngiogenesisEndothelial cell differentiationOvarian cancerHuman umbilical vein endothelial cellscancer stem-like cellsEndothelial progenitor cellsEndothelial cellscancer stem cellCancer stem cellsVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)nuclear factor kappa Bsignal transducer and activator of transcription 3
Related Topics
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Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
Shu Tang, Tong Xiang, Shuo Huang, Jie Zhou, Zhongyu Wang, Rongkai Xie, Haixia Long, Bo Zhu,