title: Expression and function of CXCR4 in human salivary gland cancers.
abstract: Salivary gland cancers (SGCs) frequently metastasize to cervical lymph nodes and distant organs. Currently, the mechanisms responsible for the metastatic behavior of SGC cells are not fully understood. We previously demonstrated that the stromal cell-derived factor-1 (SDF-1; also known as CXCL12)/CXCR4 system is involved in the establishment of metastasis in oral squamous cell carcinoma. In the present study, we investigated the role of CXCR4 in the metastatic behavior of SGCs. We examined the expression of CXCR4 mRNA and protein in human SGC cell lines by quantitative RT-PCR and western blotting, respectively. The expression of CXCR4 mRNA and protein were frequently upregulated in 5 out of 6 SGC cell lines. Functional CXCR4 expression was demonstrated by the ability of these SGC cell lines to migrate toward an SDF-1 gradient. SDF-1 rapidly activated extracellular signal-regulated kinase (ERK)1/2 in SGC cell lines. Immunohistochemical analysis revealed that CXCR4 protein expression was detected in either the nucleus or cytoplasm of cancer cells in 16 out of 20 tissues of adenoid cystic carcinoma (ACC) and in 4 out of 6 tissues of mucoepidermoid carcinoma, which are representative of SGC. Furthermore, ACC cell lines exhibited dramatic metastasis to the lung following intravenous inoculation, whereas AMD3100, a CXCR4 antagonist, significantly inhibited lung metastasis of the cells, ameliorated body weight loss and improved the survival rate of tumor-bearing nude mice. These results indicate that CXCR4 expression contributes to the metastatic potential of SGCs.
authors: Subdivision of Molecular Oral Medicine, Division of Integrated Sciences of Translational Research, Department of Oral Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, Japan. daisuke@dent.tokushima-u.ac.jp
authors: Daisuke
authors: D
authors: Uchida
authors: Nobuyuki
authors: N
authors: Kuribayashi
authors: Makoto
authors: M
authors: Kinouchi
authors: Go
authors: G
authors: Ohe
authors: Tetsuya
authors: T
authors: Tamatani
authors: Hirokazu
authors: H
authors: Nagai
authors: Youji
authors: Y
authors: Miyamoto
mesh_terms: D000818:Animals; D001596:Benzylamines; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D002448:Cell Adhesion; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D000080027:Cyclams; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D048052:Mitogen-Activated Protein Kinase 3; C088327:plerixafor