Endothelial derived factors inhibit anoikis of head and neck cancer stem cells

被引：31
作者：
Campos, Marcia S. [1 ]
Neiva, Kathleen G. [1 ]
Meyers, Kristy A. [1 ]
Krishnamurthy, Sudha [1 ]
Noer, Jacques E. [1 ,2 ,3 ]
机构：
[1] Univ Michigan, Sch Dent, Angiogenesis Res Lab, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Coll Engn, Dept Biomed Engn, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Sch Med, Dept Otolaryngol, Ann Arbor, MI 48109 USA
来源：
ORAL ONCOLOGY | 2012年 / 48卷 / 01期
关键词：
Head and neck squamous cell carcinoma; Perivascular niche; Angiogenesis; Tumor microenvironment; Metastasis; BREAST-CANCER; SELF-RENEWAL; CROSS-TALK; CARCINOMA; LINES; IDENTIFICATION; ACTIVATION; PROMOTES; TUMORS;
D O I：
10.1016/j.oraloncology.2011.09.010
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Recent evidence demonstrated that cancer stem cells reside in close proximity to blood vessels in human head and neck squamous cell carcinomas (HNSCC). These findings suggest the existence of a supporting perivascular niche for cancer stem cells. The purpose of this study was to evaluate the effect of endothelial cell-secreted factors on the behavior of head and neck cancer stem-like cells (HNCSC). HNCSC were identified by sorting UM-SCC-22A (cell line derived from a primary squamous cell carcinoma of the oropharynx) and UM-SCC-22B (derived from the metastatic lymph node of the same patient) for CD44 expression and ALDH (aldehyde dehydrogenase) activity. HNCSC (ALDH+CD44+) and control (ALDH-CD44-) cells were cultured in ultra-low attachment plates in presence of conditioned medium from primary human endothelial cells. ALDH+CD44+ generated more orospheres than control cells when cultured in suspension. The growth factor milieu secreted by endothelial cells protected HNCSC against anoikis. Mechanistic studies revealed that endothelial cell-secreted vascular endothelial growth factor (VEGF) induces proliferation of HNCSC derived from primary UM-SCC-22A, but not from the metastatic UM-SCC-22B. Likewise, blockade of VEGF abrogated endothelial cell-induced Akt phosphorylation in HNCSC derived from UM-SCC-22A while it had a modest effect in Akt phosphorylation in HNCSC from UM-SCC-22B. This study revealed that endothelial cells initiate a crosstalk that protect head and neck cancer stem cells against anoikis, and suggest that therapeutic interference with this crosstalk might be beneficial for patients with head and neck cancer. (C) 2011 Elsevier Ltd. All rights reserved.
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页码：26 / 32
页数：7
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