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Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition

Cancer Gene Therapy volume 22, pages 518–523 (2015)Cite this article

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Abstract

Bone marrow-derived endothelial progenitor cells (EPCs) migrate to and engraft at ovarian cancer sites. Understanding the interactions between ovarian cancer cells and EPCs is fundamental for determining whether to harness EPC–tumor interactions for delivery of therapeutic agents or target them for intervention. Ovarian cancer cell lines (SKOV-3 and OVCAR-3) were cultured alone or in EPC-conditioned media (EPC-CM). Migration of ovarian cancer cells was detected by transwell chamber. N-cadherin and E-cadherin expression were analyzed by real-time reverse transcription PCR and western blot. EPC-CM can increase transforming growth factor-beta (TGF-β) secretion in SKOV-3 and OVCAR-3 cells. EPC-CM induced loss of ovarian cancer cell–cell junctions, downregulation of E-cadherin, upregulation of N-cadherin and acquisition of a fibroblastic phenotype, consistent with an epithelial-to-mesenchymal transition (EMT). The specific TGF-β inhibitor SB431542 abolished the SKOV-3 and OVCAR-3 ovarian cancer cell migration induced by EPC-CM. In SKOV-3 and OVCAR-3 cells, EPC-CM downregulated E-cadherin and concurrently upregulated N-cadherin. EPC-CM upregulated the expression of transcriptional repressors of E-cadherin, Snail and Twist. Treatment with SB431542 abolished the effects of EPC-CM on the relative expression levels of cadherin, Snail and Twist. This study demonstrates that TGF-β has a role in EPC-CM-induced ovarian cancer migration by activating EMT.

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Acknowledgements

The study was supported by grants from the National Natural Science Foundation of China (no 81202039 and 81571437), the Natural Science Foundation of Heilongjiang Province, China (no. QC2012C037) and Science Foundation of Heilongjiang Province Health Department (no. 2011-134).

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  1. Y Su and L Gao: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, Cancer Hospital, Harbin Medical University, Harbin, China

    L Teng, S Peng, H Guo, H Liang, Z Xu & Y Su

  2. Department of Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China

    L Gao

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  1. L Teng
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  2. S Peng
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  3. H Guo
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  7. L Gao
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Correspondence to Y Su.

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Teng, L., Peng, S., Guo, H. et al. Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition. Cancer Gene Ther 22, 518–523 (2015). https://doi.org/10.1038/cgt.2015.45

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