Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-10-21
pubmed:abstractText
We examined the role of chemokine signaling on the lymph node metastasis of oral squamous cell carcinoma (SCC) using lymph node metastatic (HNt and B88) and nonmetastatic oral SCC cells. Of 13 kinds of chemokine receptors examined, only CXCR4 expression was up-regulated in HNt and B88 cells. CXCR4 ligand, stromal-cell-derived factor-1alpha (SDF-1alpha; CXCL12), induced characteristic calcium fluxes and chemotaxis only in CXCR4-expressing cells. CXCR4 expression in metastatic cancer tissue was significantly higher than that in nonmetastatic cancer tissue or normal gingiva. Although SDF-1alpha was undetectable in either oral SCC or normal epithelial cells, submandibular lymph nodes expressed the SDF-1alpha protein, mainly in the stromal cells, but occasionally in metastatic cancer cells. The conditioned medium from lymphatic stromal cells promoted the chemotaxis of B88 cells, which was blocked by the CXCR4 neutralization. SDF-1alpha rapidly activated extracellular signal-regulated kinase (ERK)1/2 and Akt/protein kinase B (PKB), and their synthetic inhibitors attenuated the chemotaxis by SDF-1alpha. SDF-1alpha also activated Src family kinases (SFKs), and its inhibitor PP1 diminished the SDF-1alpha-induced chemotaxis and activation of both ERK1/2 and Akt/PKB. These results indicate that SDF-1/CXCR4 signaling may be involved in the establishment of lymph node metastasis in oral SCC via activation of both ERK1/2 and Akt/PKB induced by SFKs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CXCL12 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL12, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC, http://linkedlifedata.com/resource/pubmed/chemical/Cxcl12 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CXCR4
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-302
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14567988-Animals, pubmed-meshheading:14567988-Blotting, Western, pubmed-meshheading:14567988-Calcium, pubmed-meshheading:14567988-Carcinoma, Squamous Cell, pubmed-meshheading:14567988-Cell Movement, pubmed-meshheading:14567988-Chemokine CXCL12, pubmed-meshheading:14567988-Chemokines, CXC, pubmed-meshheading:14567988-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:14567988-Humans, pubmed-meshheading:14567988-Lymphatic Metastasis, pubmed-meshheading:14567988-Mice, pubmed-meshheading:14567988-Mice, Inbred BALB C, pubmed-meshheading:14567988-Mice, Nude, pubmed-meshheading:14567988-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:14567988-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:14567988-Mitogen-Activated Protein Kinases, pubmed-meshheading:14567988-Mouth Neoplasms, pubmed-meshheading:14567988-Phosphorylation, pubmed-meshheading:14567988-Precipitin Tests, pubmed-meshheading:14567988-Protein-Serine-Threonine Kinases, pubmed-meshheading:14567988-Proto-Oncogene Proteins, pubmed-meshheading:14567988-Proto-Oncogene Proteins c-akt, pubmed-meshheading:14567988-Receptors, CXCR4, pubmed-meshheading:14567988-Signal Transduction
pubmed:year
2003
pubmed:articleTitle
Possible role of stromal-cell-derived factor-1/CXCR4 signaling on lymph node metastasis of oral squamous cell carcinoma.
pubmed:affiliation
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto, Tokushima 770-8504, Japan. daisuke@dent.tokushima-u.ac.jp
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't