In vivo invasion of head and neck squamous cell carcinoma cells does not require macrophages

Tatiana Smirnova, Alfred Adomako, Joseph Locker, Nico Van Rooijen, Michael B. Prystowsky, Jeffrey E. Segall

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2857-2865
Number of pages9
JournalAmerican Journal of Pathology
Volume178
Issue number6
DOIs
StatePublished - Jun 2011

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Macrophages
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Neoplasms
Mouth Floor
Chemokine CXCL12
Protease Inhibitors
Transcriptional Activation
Carcinoma, squamous cell of head and neck
Intercellular Signaling Peptides and Proteins
Tumor Necrosis Factor-alpha
Ligands
Enzymes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

In vivo invasion of head and neck squamous cell carcinoma cells does not require macrophages. / Smirnova, Tatiana; Adomako, Alfred; Locker, Joseph; Van Rooijen, Nico; Prystowsky, Michael B.; Segall, Jeffrey E.

In: American Journal of Pathology, Vol. 178, No. 6, 06.2011, p. 2857-2865.

Research output: Contribution to journalArticle

Smirnova, Tatiana ; Adomako, Alfred ; Locker, Joseph ; Van Rooijen, Nico ; Prystowsky, Michael B. ; Segall, Jeffrey E. / In vivo invasion of head and neck squamous cell carcinoma cells does not require macrophages. In: American Journal of Pathology. 2011 ; Vol. 178, No. 6. pp. 2857-2865.
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