Downregulation of transgelin blocks interleukin-8 utilization and suppresses vasculogenic mimicry in breast cancer cells
- Authors
- Aikins, Anastasia R.; Kim, MiJung; Raymundo, Bernardo; Kim, Chan-Wha
- Issue Date
- 3월-2017
- Publisher
- SAGE PUBLICATIONS LTD
- Keywords
- Vasculogenic mimicry; transgelin; cancer stem cells; interleukin-8; endothelial markers; breast cancer
- Citation
- EXPERIMENTAL BIOLOGY AND MEDICINE, v.242, no.6, pp.573 - 583
- Indexed
- SCIE
SCOPUS
- Journal Title
- EXPERIMENTAL BIOLOGY AND MEDICINE
- Volume
- 242
- Number
- 6
- Start Page
- 573
- End Page
- 583
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/84270
- DOI
- 10.1177/1535370216685435
- ISSN
- 1535-3702
- Abstract
- Vasculogenic mimicry (VM) is a non-classical mechanism recently described in many tumors, whereby cancer cells, rather than endothelial cells, form blood vessels. Transgelin is an actin-binding protein that has been implicated in multiple stages of cancer development. In this study, we investigated the role of transgelin in VM and assessed its effect on the expression of endothelial and angiogenesis-related genes during VM in MDA-MB-231 breast cancer cells. We confirmed the ability of MDA-MB-231 cells to undergo VM through a tube formation assay. Flow cytometry analysis revealed an increase in the expression of the endothelial-related markers VE-cadherin and CD34 in cells that underwent VM, compared with those growing in a monolayer, which was confirmed by immunocytochemistry. We employed siRNA to silence transgelin, and knockdown efficiency was determined by western blot analyses. Downregulation of transgelin suppressed cell proliferation and tube formation, but increased IL-8 levels in Matrigel cultures. RT-PCR analyses revealed that the expression of IL-8, VE-cadherin, and CD34 was unaffected by transgelin knockdown, indicating that increased IL-8 expression was not due to enhanced transcriptional activity. More importantly, the inhibition of IL-8/CXCR2 signaling also resulted in suppression of VM with increased IL-8 levels, confirming that increased IL-8 levels after transgelin knockdown was due to inhibition of IL-8 uptake. Our findings indicate that transgelin regulates VM by enhancing IL uptake. These observations are relevant to the future development of efficient antivascular agents.
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Collections - College of Life Sciences and Biotechnology > Division of Life Sciences > 1. Journal Articles
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