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The Ron receptor tyrosine kinase positively regulates angiogenic chemokine production in prostate cancer cells

Oncogene volume 29, pages 214–226 (2010)Cite this article

Abstract

Overexpression of the Ron receptor tyrosine kinase has recently been shown in a wide variety of human cancers. However, no studies have examined Ron receptor expression or function during prostate tumorigenesis. In this study we report that Ron is highly expressed in human prostate adenocarcinoma and metastatic lymph nodes when compared with normal prostate or benign prostate hyperplasia. Furthermore, we show that Ron is overexpressed in PC-3 and DU145 prostate cancer cell lines, and that the levels of angiogenic chemokines produced by prostate cancer cells positively correlate with Ron expression. The knockdown of Ron in PC-3 or DU145 cells results in a significant decrease in angiogenic chemokine production and is associated with a decreased activation of the transcription factor nuclear factor-κB (NF-κB). Moreover, exogenous overexpression of Ron in LNCaP cells is sufficient to induce a significant increase in angiogenic chemokines that can be abrogated by inhibition of NF-κB signaling. Given that the function of angiogenic chemokines is important in the development of new blood vessels, we also examined the ability of Ron to modulate endothelial cell migration. Our data show that knockdown of Ron in prostate cancer cells results in significantly less endothelial cell chemotaxis when compared with Ron-expressing cells in vitro as well as in reduced tumor growth and decreased microvessel density after orthotopic transplantation into the prostate in vivo. In total, our data suggest that the Ron receptor is important in modulating prostate tumor growth by modulating angiogenic chemokine production and subsequent endothelial cell recruitment.

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Acknowledgements

We thank Sandy Schwemberger for her assistance with the flow cytometry experiments as well as Sarah Kader for her technical contributions. This work was supported by Public Health Services Grants CA-125370 (SEW) from the National Institutes of Health, and by grant project no. PC060821 (MNT) from the Department of Defense Congressionally Directed Medical Research Programs.

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  1. Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    M N Thobe, D Gurusamy, P Pathrose & S E Waltz

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  1. M N Thobe
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Correspondence to S E Waltz.

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Thobe, M., Gurusamy, D., Pathrose, P. et al. The Ron receptor tyrosine kinase positively regulates angiogenic chemokine production in prostate cancer cells. Oncogene 29, 214–226 (2010). https://doi.org/10.1038/onc.2009.331

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