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Tumor-derived mural-like cells coordinate with endothelial cells: role of YKL-40 in mural cell-mediated angiogenesis

Oncogene volume 33, pages 2110–2122 (2014)Cite this article

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Abstract

Tumor neo-vasculature is characterized by spatial coordination of endothelial cells with mural cells, which delivers oxygen and nutrients. Here, we explored a key role of the secreted glycoprotein YKL-40, a mesenchymal marker, in the interaction between endothelial cells and mesenchymal mural-like cells for tumor angiogenesis. Xenotransplantation of tumor-derived mural-like cells (GSDCs) expressing YKL-40 in mice developed extensive and stable blood vessels covered with more GSDCs than those in YKL-40 gene knockdown tumors. YKL-40 expressed by GSDCs was associated with increased interaction of neural cadherin/β-catenin/smooth muscle alpha actin; thus, mediating cell-cell adhesion and permeability. YKL-40 also induced the interaction of vascular endothelial cadherin/β-catenin/actin in endothelial cells (HMVECs). In cell co-culture systems, YKL-40 enhanced both GSDC and HMVEC contacts, restricted vascular leakage, and stabilized vascular networks. Collectively, the data inform new mechanistic insights into the cooperation of mural cells with endothelial cells induced by YKL-40 during tumor angiogenesis, and also enhance our understanding of YKL-40 in both mural and endothelial cell biology.

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Abbreviations

N-cadherin:

neural cadherin

shRNA:

short-hairpin RNA gene knockdown

VE-cadherin:

vascular endothelial cadherin

VEGF:

vascular endothelial growth factor

YKL-40:

human cartilage glycoprotein-39 or Chitinase-3-like-1.

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Acknowledgements

This work was supported by NCI R01 CA120659 and CEAR grant, John Adams Innovation Institute, Massachusetts (RS).

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Authors and Affiliations

  1. Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA, USA

    R Francescone & R Shao

  2. Graduate School, Khon Khaen University, Khon Khaen, Thailand

    N Ngernyuang

  3. Pioneer Valley Life Sciences Institute, Springfield, MA, USA

    W Yan, B Bentley & R Shao

  4. Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, USA

    R Shao

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  1. R Francescone
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  2. N Ngernyuang
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Correspondence to R Shao.

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Francescone, R., Ngernyuang, N., Yan, W. et al. Tumor-derived mural-like cells coordinate with endothelial cells: role of YKL-40 in mural cell-mediated angiogenesis. Oncogene 33, 2110–2122 (2014). https://doi.org/10.1038/onc.2013.160

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