1. In vivo invasion of head and neck squamous cell carcinoma cells does not require macrophages.
- Author
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Smirnova T, Adomako A, Locker J, Van Rooijen N, Prystowsky MB, and Segall JE
- Subjects
- ADAM Proteins metabolism, ADAM17 Protein, Animals, Cell Line, Tumor, Chemokine CXCL12 pharmacology, Disease Models, Animal, Epidermal Growth Factor pharmacology, ErbB Receptors metabolism, Humans, Macrophages drug effects, Mice, Mice, Nude, Neoplasm Invasiveness, Signal Transduction drug effects, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms pathology, Macrophages pathology
- Abstract
Invasion of tumor cells into the local stroma is an important component in cancer progression. Here we report studies of the in vivo invasion of head and neck squamous cell carcinoma (HNSCC) cells in response to applied gradients of a growth factor [epidermal growth factor (EGF)] and a chemokine (CXCL12), using orthotopic floor-of-mouth models. Analysis of the invading cells indicated that >75% of them were tumor cells, about 15% macrophages, and <10% were unidentified. Surprisingly, although macrophages invaded together with tumor cells, macrophage contributions were not required for HNSCC invasion. CXCL12-induced in vivo invasion of HNSCC cells was also observed and found to occur via a unidirectional transactivation of epidermal growth factor receptor (EGFR) through CXCR4. Inhibition of tumor necrosis factor-α-converting enzyme using TNF-α protease inhibitor-2 selectively inhibited CXCL12-induced invasion but not EGF-induced invasion, consistent with CXCL12 activation of EGFR via release of EGFR ligands., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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