Gefitinib ('Iressa'), an epidermal growth factor receptor tyrosine kinase inhibitor, mediates the inhibition of lymph node metastasis in oral cancer cells.
High expression of epidermal growth factor receptor (EGFR) is frequently observed in many solid tumor types including oral squamous cell carcinomas (OSCC). This study investigated whether treatment with gefitinib ('Iressa'), an EGFR-tyrosine kinase inhibitor, would inhibit the metastatic spread in OSCC cells. This was evaluated using orthotopic xenografts of highly metastatic OSCC. Metastasis was observed in six of 13 gefitinib treated animals (46.2%), compared with all of 12 control animals (100%). After exposure to gefitinib, OSCC cells showed a marked reduction in cell adhesion ability to fibronectin and in the expression of integrin alpha3, alphav, beta1, beta4, beta5 and beta6.
Shintani
Satoru
S
Department of Oral and Maxillofacial Surgery, Ehime University School of Medicine, 454 Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. satoru@m.ehime-u.ac.jp
Li
Chunnan
C
Mihara
Mariko
M
Nakashiro
Koh-ichi
K
Hamakawa
Hiroyuki
H
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000187:drug effects; D000077156:Gefitinib; D049452:Green Fluorescent Proteins; D016023:Integrins / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects* / Q000378:metabolism; D008207:Lymphatic Metastasis; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use*; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005353:Fibronectins; D016023:Integrins; D008164:Luminescent Proteins; D011799:Quinazolines; D049452:Green Fluorescent Proteins; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D000077156:Gefitinib