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CD44+/CD24− breast cancer cells isolated from MCF-7 cultures exhibit enhanced angiogenic properties

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Abstract

Background

Recent studies suggest that the relationship between cancer stem cells (CSCs) and the vascular niche may be bidirectional; the niche can support the growth and renewal of CSCs, and CSCs may contribute to the maintenance of the niche. There is little knowledge concerning the role of breast cancer stem cells in promoting tumor angiogenesis.

Aim

For human breast cancers, CSCs have been shown to be associated with a CD44+/CD24− phenotype. We investigated the potential activities of CD44+/CD24− breast cancer stem cells in promoting tumor angiogenesis.

Methods

The expression of pro-angiogenic genes was determined by quantitative real-time RT-PCR. Endothelial cell migration assays were employed to evaluate effects of conditioned media from CD44+/CD24− on human umbilical vein endothelial cells. A chorioallantoic membrane (CAM) assay was used to study the potential of CD44+/CD24− cells to promote angiogenesis.

Results

In our study, CD44+/CD24− cells expressed elevated levels of pro-angiogenic factors compared with CD44+/CD24+ cells. CD44+/CD24− cell-conditioned media significantly increased endothelial cell migration. Breast cancer cell lines enriched with CD44+/CD24− cells were more pro-angiogenic in the CAM assay than those lacking a CD44+/CD24− subpopulation. CD44+/CD24− cells sorted from MCF-7 cell lines were more pro-angiogenic in a CAM assay than CD44+/CD24+ cells. Furthermore, the VEGF concentration was significantly higher in CD44+/CD24− cell-conditioned media than in CD44+/CD24+ cell-conditioned media. The pro-angiogenic effect of CD44+/CD24− cells on endothelial cells was abolished by bevacizumab.

Conclusion

Our findings demonstrate that CD44+/CD24− breast cancer stem cells have substantial pro-angiogenic potential and activity. This provides new insights to explore in the development of targeted therapies.

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Abbreviations

CSCs:

Cancer stem cells

HUVECs:

Human umbilical vein endothelial cells

FCS:

Fetal calf serum

PBS:

Phosphate-buffered saline

CAM:

Chorioallantoic membrane

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Acknowledgments

We thank Dr. Hongxia Li (Department of Medical Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China) for constructive advices on the manuscript. This work was supported by Beijing Medical Oncology Leadership grant 2009-2-16 from Beijing Municipal Government Health Bureau.

Conflict of interest

None.

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Author notes

  1. Jun Ren

    Present address: Capital Medical University Cancer Center, Beijing Shijitan Hospital, 10 Tieyilu, Beijing, 100038, China

Authors and Affiliations

  1. Duke-PKU Cancer Program, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Medical Oncology and Immunotherapy, Beijing Cancer Hospital and Institute, Peking University School of Oncology, Peking University Cancer Hospital, 52 Fucheng Rd, Beijing, 100142, China

    Hongmei Sun, Jun Jia, Xiaoli Wang, Bo Ma, Lijun Di, Guohong Song & Jun Ren

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  1. Hongmei Sun
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Correspondence to Jun Ren.

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Sun, H., Jia, J., Wang, X. et al. CD44+/CD24− breast cancer cells isolated from MCF-7 cultures exhibit enhanced angiogenic properties. Clin Transl Oncol 15, 46–54 (2013). https://doi.org/10.1007/s12094-012-0891-2

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  • DOI: https://doi.org/10.1007/s12094-012-0891-2

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