Article

Onoue T, Uchida D, Begum NM, Tomizuka Y, Yoshida H, Sato MEpithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells. Int J Oncol 29: 1133-1138

Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
International Journal of Oncology (Impact Factor: 3.03). 12/2006; 29(5):1133-8. DOI: 10.3892/ijo.29.5.1133
Source: PubMed

ABSTRACT

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.

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    • "EMT refers to critical events in tumor progression including invasion and metastasis by which cancer cells acquire a fibroblast-like phenotype. Indeed, it has been reported that SDF-1/ CXCR4 promotes EMT and progression of colorectal cancer (Hu et al., 2014), oral squamous cell carcinoma, (Onoue et al., 2006), hepatocellular carcinoma (Li et al., 2014), and pancreatic cancer cells (Li et al., 2012). Nevertheless, cancer-associated stromal cells are heavily stained with SDF-1 suggesting an important role of stromal cell-derived SDF-1 in skin cancer progression including the possibility of promoting cancer cell EMT. "
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    • "In addition to MMP stimulation, CXCR4 and CXCL12 interaction induces epithelial-mesenchymal transition (EMT) in HNSCC cells. It appears that the crosstalk between CXCL12 and its receptor might be involved in the lymph node metastasis of HNSCC cells 173.In addition to CXCL12, it was reported that HNSCC derived from a lymph node metastasis, but not from a synchronous primary tumor, secreted CXCL5 174. Furthermore, CXCL5 also stimulated cell proliferation and the in vitro invasion of metastatic HNSCC cells. "
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