Abstract 3879: Crosstalk initiated by endothelial cells endows head and neck cancer stem cells with an invasive phenotype

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 3879
• Main Authors: Kim, Hong S., Zhang, Zhaocheng, Warner, Kristy A., Finkel, Kelsey A., Adams, April, Nor, Jacques E.
• Format: Journal Article
• Language: English
• Published: 01-10-2014
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-3879

Abstract
Head and neck squamous cell carcinomas contain a sub-population of uniquely tumorigenic cells (named cancer stem cells) that are thought to participate in metastatic dissemination. We have previously shown that head and neck cancer stem cells (HNCSC) can be identified as ALDHhighCD44high and reside within the perivascular niche, in close proximity to blood vessels. Therefore, it is possible that a crosstalk between HNCSC and endothelial cells plays a functional role in metastatic spread. Here, we hypothesize that factors secreted by endothelial cells enhance motility and invasiveness of HNCSC. We observed that endothelial cell-derived factors induced epithelial-mesenchymal transition (EMT) of unsorted head and neck squamous cell carcinoma (HNSCC) cells, as demonstrated by decreased expression of epithelial markers (e.g. Desmoplakin), enhanced expression mesenchymal cell markers (e.g. Vimentin) and transcriptional regulators of EMT (e.g. Snail), and enhanced migration of these cells. Further, endothelial cell-secreted factors enhanced the orosphere forming-ability of HNSCC plated in ultra-low attachment plates, enhanced the fraction of ALDHhighCD44high cells, and expression of Bmi-1. Similarly, HNCSC had increased number of orospheres and enhanced motility in the presence of endothelial cell-derived factors. Taken together, these data indicate that a crosstalk initiated by endothelial cells endows head and neck cancer cells with high motility and a stem-like phenotype, and suggest that endothelial cells may play an active role in the initial steps of metastatic spread. Support for this work was provided by grant R01-DE21139 from the NIH/NIDCR, and grant P50-CA97248 (University of Michigan Head Neck SPORE) from the NIH/NCI.
Citation Format: Hong S. Kim, Zhaocheng Zhang, Kristy A. Warner, Kelsey A. Finkel, April Adams, Jacques E. Nor. Crosstalk initiated by endothelial cells endows head and neck cancer stem cells with an invasive phenotype. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3879. doi:10.1158/1538-7445.AM2014-3879