title: In vivo invasion of head and neck squamous cell carcinoma cells does not require macrophages.
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.
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Smirnova
authors.forename: Alfred
authors.initials: A
authors.lastname: Adomako
authors.forename: Joseph
authors.initials: J
authors.lastname: Locker
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Michael B
authors.initials: MB
authors.lastname: Prystowsky
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Segall
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000494:pharmacology; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054377:Chemokine CXCL12; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein