Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells.
Epithelial-mesenchymal transition (EMT) refers to critical events occasionally observed during tumor progression, including invasion and metastasis, by which cancer cells acquire a fibroblast-like phenotype. Since the stromal cell-derived factor-1 (SDF-1)/CXCR4 system can facilitate lymph node metastasis in oral squamous cell carcinoma (SCC), we have explored the possibility that this system might be involved in EMT. Oral SCC cells, B88 and HNt, which have functional CXCR4 and lymph node metastatic potential, were found to lose their epithelial cell morphology due to SDF-1. In this context, the downregulation of epithelial markers, cytokeratin, E-cadherin and beta-catenin, and the upregulation of mesenchymal marker, vimentin and snail were detected. Furthermore, upregulation of vimentin by treatment with SDF-1 was impaired by phosphatidylinositol 3 kinase (PI3K) inhibitor Wortmannin, but not by mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor U0126. In the type I collagen embedding culture, SDF-1-treated B88 cells formed protruding extensions, but the effect was impaired by treatment with Wortmannin. These results suggested that EMT induced by the SDF-1/CXCR4 system might be involved in the lymph node metastasis of oral SCCs via activation of PI3K-Akt/PKB pathway.
Onoue
Tomitaro
T
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
Uchida
Daisuke
D
Begum
Nasima Mila
NM
Tomizuka
Yoshifumi
Y
Yoshida
Hideo
H
Sato
Mitsunobu
M
D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000556:secondary*; D018929:Cell Culture Techniques; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism* / Q000494:pharmacology; D015536:Down-Regulation; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis; D008648:Mesoderm / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D009062:Mouth Neoplasms / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism
D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D047428:Protein Kinase Inhibitors; D019718:Receptors, CXCR4; D014746:Vimentin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt