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CD133+ cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer

Oncogene volume 32, pages 544–553 (2013)Cite this article

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Abstract

Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. In the study we demonstrated that CD133 expression was the highest in triple-negative (TN) breast cancer specimens. Importantly, VM showed statistical correlation with CD133+ expression. The presence of the close relationship between VM and CD133+ expression might be central for TN tumor relapse and progression. The TN breast cancer cell line, MDA-MB-231 cells developed a range of colony morphologies paralleling the holoclone, meroclone and paraclone morphologies produced by normal keratinocytes and other epithelial cancer cell lines when plated at clonal densities. Holoclone cells were capable of forming more colonies on soft agar than meroclone cells and paraclone cells, suggesting that holoclone cells had higher self-renew potential and might harbors cancer stem cells (CSCs) subpopulation. Strikingly, it was holoclone that displayed CD133+ phenotype and formed VM. In addition, holoclone acquired endothelial cell marker vascular endothelial-cadherin expression and upregulated VM mediators matrix metalloproteinase (MMP)-2 and MMP-9 expression. The subpopulation with holoclone morphology, CD133+ phenotype and CSCs characteristics might have the capacity of transdifferentiation and contributed to VM in TN breast cancer. The related molecular pathways may be used as novel therapeutic targets for the inhibition of angiogenesis and metastasis in TN breast carcinoma.

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Abbreviations

3D:

three dimensional

CFE:

colony forming efficiency

CSCs:

cancer stem cells

MMPs:

matrix metalloproteinases

PAS:

periodic acid-Schiff

TN:

triple-negative

VE:

vascular endothelial

VM:

vasculogenic mimicry

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Acknowledgements

This work was partly supported by a Grant from Key project of the National Natural Science Foundation of China (No. 30830049), the International Cooperation project of China-Sweden (No. 09ZCZDSF04400), the National Natural Science Foundation of China (No. 81172046 and No. 81173091) and the 973 Program from the Ministry of Science and Technology of China (No. 2009CB918903).

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Author notes

  1. T J Liu, B C Sun and X L Zhao: These authors equally contribute to this study

Authors and Affiliations

  1. Department of Pathology, Tianjin Medical University, Tianjin, China

    T J Liu, B C Sun, X L Zhao, X M Zhao, T Sun, Q Gu, Z Yao, X Y Dong, N Zhao & N Liu

  2. Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China

    B C Sun

  3. Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin, China

    B C Sun, X L Zhao & Q Gu

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  1. T J Liu
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Correspondence to B C Sun.

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Liu, T., Sun, B., Zhao, X. et al. CD133+ cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer. Oncogene 32, 544–553 (2013). https://doi.org/10.1038/onc.2012.85

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