Endothelial-derived interleukin-6 induces cancer stem cell motility by generating a chemotactic gradient towards blood vessels
| Autor: | Euisik Yoon, Alexander T. Pearson, Zhaocheng Zhang, Manoela Domingues Martins, Kristy A. Warner, Jacques E. Nör, Vivian Petersen Wagner, April Andrews, Hong Sun Kim, Yu Chih Chen, Zhixiong Zhang, Felipe Nör |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
cancer stem cells
0301 basic medicine Pathology medicine.medical_specialty epithelial-mesenchymal transition migration head and neck squamous cell carcinoma Metastasis 03 medical and health sciences 0302 clinical medicine Cancer stem cell Carcinoma medicine metastasis Epithelial–mesenchymal transition biology business.industry CD44 Cancer medicine.disease Head and neck squamous-cell carcinoma 3. Good health 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis biology.protein Cancer research business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.22225 |
| Popis: | // Hong Sun Kim 1 , Yu-Chih Chen 2, 6 , Felipe Nor 1, 3 , Kristy A. Warner 1 , April Andrews 1 , Vivian P. Wagner 3, 4 , Zhaocheng Zhang 1 , Zhixiong Zhang 2 , Manoela D. Martins 3, 4 , Alexander T. Pearson 1, 5, 6 , Euisik Yoon 2, 7 and Jacques E. Nor 1, 6, 7, 8 1 Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA 2 Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA 3 Department of Oral Pathology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil 4 Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA 5 Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA 6 Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA 7 Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA 8 Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, MI, USA Correspondence to: Jacques E. Nor, email: jenor@umich.edu Keywords: cancer stem cells; epithelial-mesenchymal transition; migration; head and neck squamous cell carcinoma; metastasis Received: August 11, 2017 Accepted: October 13, 2017 Published: November 01, 2017 ABSTRACT Recent evidence suggests that the metastatic spread of head and neck squamous cell carcinomas (HNSCC) requires the function of cancer stem cells endowed with multipotency, self-renewal, and high tumorigenic potential. We demonstrated that cancer stem cells reside in perivascular niches and are characterized by high aldehyde dehydrogenase (ALDH) activity and high CD44 expression (ALDH high CD44 high ) in HNSCC. Here, we hypothesize that endothelial cell-secreted interleukin-6 (IL-6) contributes to tumor progression by enhancing the migratory phenotype and survival of cancer stem cells. Analysis of tissue microarrays generated from the invasive fronts of 77 HNSCC patients followed-up for up to 11 years revealed that high expression of IL-6 receptor (IL-6R) (p=0.0217) or co-receptor gp130 (p=0.0422) correlates with low HNSCC patient survival. We observed that endothelial cell-secreted factors induce epithelial to mesenchymal transition (EMT) and enhance invasive capacity of HNSCC cancer stem cells. Conditioned medium from CRISPR/Cas9-mediated IL-6 knockout primary human endothelial cells is less chemotactic for cancer stem cells in a microfluidics-based system than medium from control endothelial cells (p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|