Tie-2 regulates the stemness and metastatic properties of prostate cancer cells

Tang, Kai-Dun, Holzapfel, Boris M., Liu, Ji, Lee, Terence Kin-Wah, Ma, Stephanie, Jovanovic, Lidija, An, Jiyuan, Russell, Pamela J., Clements, Judith A., Hutmacher, Dietmar W., & Ling, Ming-Tat (2015) Tie-2 regulates the stemness and metastatic properties of prostate cancer cells. Oncotarget, 7(3), pp. 2572-2584.

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Abstract

Ample evidence supports that prostate tumor metastasis originates from a rare population of cancer cells, known as cancer stem cells (CSCs). Unfortunately, little is known about the identity of these cells, making it difficult to target the metastatic prostate tumor. Here, for the first time, we report the identification of a rare population of prostate cancer cells that express the Tie-2 protein. We found that this Tie-2High population exists mainly in prostate cancer cell lines that are capable of metastasizing to the bone. These cells not only express a higher level of CSC markers but also demonstrate enhanced resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an autocrine loop for the maintenance of prostate CSCs. More importantly, we found that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low population to both osteoblasts and endothelial cells. Moreover, only the Tie-2High, but not the Tie-2Low cells developed tumor metastasis in vivo when injected at a low number. Taken together, our data suggest that Tie-2 may play an important role during the development of prostate tumor metastasis.

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ID Code: 90512
Item Type: Journal Article
Refereed: Yes
Keywords: Tie-2, cancer stem cells, metastasis, prostate cancer
DOI: 10.18632/oncotarget.3950
ISSN: 1949-2553
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Funding:
Copyright Owner: Copyright 2015 Impact Journals LLC
Copyright Statement: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Deposited On: 22 Nov 2015 22:58
Last Modified: 18 Apr 2016 02:38

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