TY - JOUR
T1 - In vivo invasion of head and neck squamous cell carcinoma cells does not require macrophages
AU - Smirnova, Tatiana
AU - Adomako, Alfred
AU - Locker, Joseph
AU - Van Rooijen, Nico
AU - Prystowsky, Michael B.
AU - Segall, Jeffrey E.
N1 - Funding Information:
Supported by grants from the NIH ( CA77522 and CA1000324 to J.E.S.) and the Department of Pathology. J.E.S. is the Betty and Sheldon Feinberg Senior Faculty Scholar in Cancer Research. Iressa (gefitinib) was provided by AstraZeneca.
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2011.02.030
DO - 10.1016/j.ajpath.2011.02.030
M3 - Article
C2 - 21641405
AN - SCOPUS:79959382602
SN - 0002-9440
VL - 178
SP - 2857
EP - 2865
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -