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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-11-16
pubmed:abstractText
Recently, it has been suggested that chemokine/receptor interactions determine the destination of the invasive tumor cells in several types of cancer. It has also been proposed that the stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4 system might be involved lymph node metastasis in oral squamous cell carcinoma (SCC). In order to further clarify the role of the SDF-1/CXCR4 system in oral SCC, we generated CXCR4 stable transfectants (IH-CXCR4) using oral SCC cells, and compared them to IH, which did not express CXCR4 and which did not have lymph node metastatic potentials in vivo. We introduced enhanced green fluorescent protein (GFP) fused-CXCR4 into IH cells, and detected the GFP fluorescence in the cytoplasm and cell membrane in approximately 60% of the G418-resistant cells. This bulk-transfectant expressed a high level of CXCR4 mRNA and protein, and exhibited the characteristic calcium fluxes and chemotactic activity observed in treatment with SDF-1. SDF-1 biphasically activated extracellular signal-regulated kinase (ERK)1/2, but continuously activated Akt/protein kinase B (PKB) in IH-CXCR4 cells. Most importantly, IH-CXCR4 cells frequently metastasized to the cervical lymph node, but not to the distant organs in the orthotopic inoculation of nude mice. Furthermore, these lymph node metastases were inhibited by the treatment of a mitogen-activated protein kinase/ERK kinase inhibitor, U0126, or a phosphatidylinositol 3 kinase inhibitor, wortmannin. These results indicate that SDF-1/CXCR4 signaling mediates the establishment of lymph node metastasis in oral SCC via ERK1/2 or Akt/PKB pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1538-46
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15492752-Animals, pubmed-meshheading:15492752-Calcium, pubmed-meshheading:15492752-Carcinoma, Squamous Cell, pubmed-meshheading:15492752-Cell Line, Tumor, pubmed-meshheading:15492752-Chemokine CXCL12, pubmed-meshheading:15492752-Chemokines, CXC, pubmed-meshheading:15492752-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15492752-Green Fluorescent Proteins, pubmed-meshheading:15492752-Lymphatic Metastasis, pubmed-meshheading:15492752-Mice, pubmed-meshheading:15492752-Mice, Inbred BALB C, pubmed-meshheading:15492752-Mice, Nude, pubmed-meshheading:15492752-Mouth Neoplasms, pubmed-meshheading:15492752-Receptors, CXCR4, pubmed-meshheading:15492752-Recombinant Fusion Proteins, pubmed-meshheading:15492752-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15492752-Transfection, pubmed-meshheading:15492752-Transplantation, Heterologous
pubmed:year
2004
pubmed:articleTitle
Acquisition of lymph node, but not distant metastatic potentials, by the overexpression of CXCR4 in human oral squamous cell carcinoma.
pubmed:affiliation
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Kuramoto, Tokushima, Japan. daisuke@dent.tokushima-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't