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ABSTRACT: Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. The present study was designed to examine the expression of chemokine receptor CCR7 in oral squamous cell carcinoma (OSCC), and to investigate the possible role of CCR7/CCL21 interaction in neck lymph node metastasis of OSCC. By using immunohistochemistry, RT-PCR and Western Blot, expression of CCR7 was examined in 85 cases of oral squamous cell carcinoma, and Tca8113 and ACC cell lines. CCL21-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber. In vitro adhesion assay was shown for banding of tumor cell lines to submandibular lymph nodes with or without anti-CCR7 antibody treatment. Immunohistochemical staining showed 65.9% (56/85) of positive CCR7 expression in OSCC tissues. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P=0.015) and was also associated with tumor size (P=0.014), and clinical stage (P=0.009). RT-PCR and Western Blot also confirmed positive CCR7 expression in oral squamous cell carcinoma and Tca8113 cell line, and negative CCR7 expression in normal oral mucosa and ACC cell line. CCL21 stimulation increased the ability of CCR7-positive Tca8113 cells passing through the Matrigel membrane. CCR7-positive Tca8113 cells also showed stronger adhesion to lymph nodes, which could be partly blocked by anti-CCR7 antibody incubation. These results indicated that the chemotactic CCR7/CCL21 interaction may be a possible mechanism for induction of directional lymph node metastasis by oral squamous cell carcinoma.
Oral Oncology 09/2008; 45(6):480-5. · 2.86 Impact Factor
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ABSTRACT: Eph-ephrin binding has been linked to tumor biology and VEGF has been reported to participate in the tumor angiogenesis regulated by Eph-ephrin. The present study was designed to evaluate the expression of EphA2 and VEGF in relation to angiogenesis and clinical outcome in squamous cell carcinoma of oral tongue. Immunohistochemical staining was used to determine the protein expression levels of EphA2 and VEGF in 59 surgically resected tongue carcinomas and 10 tumor-free mucosas. In all cases, microvessel density (MVD) was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. Both EphA2 and VEGF staining activities in squamous cell carcinoma of oral tongue were more significant than those in normal mucosa (P<0.01). MVD had significant correlations with EphA2 and VEGF expression (P<0.01). The EphA2, VEGF, and MVD were significantly correlated with tumor size, clinical stage, lymph invasion, recurrence, and distant metastasis (P<0.05). Multivariate analysis showed EphA2, VEGF expression, MVD, and clinical stage had an independent prognostic effect on overall survival. We conclude that the overexpression of EphA2 and VEGF are related to malignancy in squamous cell carcinoma of oral tongue. Clinical outcomes raised the possibility that the overexpression of those proteins might contribute to tumor angiogenesis and have prognostic value in tongue cancer.
Oral Oncology 05/2008; 44(12):1110-7. · 2.86 Impact Factor
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ABSTRACT: UDP-glucose pyrophosphorylase (UGPase) catalyzes the reversible production of glucose-1-phosphate and UTP to UDP-glucose and pyrophosphate. The rice (Oryza sativa) genome contains two homologous UGPase genes, Ugp1 and Ugp2. We report a functional characterization of rice Ugp1, which is expressed throughout the plant, with highest expression in florets, especially in pollen during anther development. Ugp1 silencing by RNA interference or cosuppression results in male sterility. Expressing a double-stranded RNA interference construct in Ugp1-RI plants resulted in complete suppression of both Ugp1 and Ugp2, together with various pleiotropic developmental abnormalities, suggesting that UGPase plays critical roles in plant growth and development. More importantly, Ugp1-cosuppressing plants contained unprocessed intron-containing primary transcripts derived from transcription of the overexpression construct. These aberrant transcripts undergo temperature-sensitive splicing in florets, leading to a novel thermosensitive genic male sterility. Pollen mother cells (PMCs) of Ugp1-silenced plants appeared normal before meiosis, but during meiosis, normal callose deposition was disrupted. Consequently, the PMCs began to degenerate at the early meiosis stage, eventually resulting in complete pollen collapse. In addition, the degeneration of the tapetum and middle layer was inhibited. These results demonstrate that rice Ugp1 is required for callose deposition during PMC meiosis and bridges the apoplastic unloading pathway and pollen development.
The Plant Cell 03/2007; 19(3):847-61. · 8.99 Impact Factor
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ABSTRACT: Uridine diphosphate (UDP)-glucose pyrophosphorylases (UGPases, EC 2.7.7.9) are key enzymes in plant carbohydrate metabolism and cell-wall biosynthesis, catalyzing the reversible production of glucose-1-phosphate and uridine triphosphate from UDP-glucose and pyrophosphate. In the study presented here, two-dimensional gel electrophoresis followed by peptide sequencing analysis using nanospray electrospray ionization tandem mass spectrometry showed that rice (Oryza sativa L.) UGPase undergoes N-terminal acetylation, which may be a conserved modification of plant UGPases. We also obtained indications, using two-dimensional gel electrophoresis in combination with western blot analysis, that multiple isoforms of UGPase are present in rice in vivo and are regulated tissue-specifically. The rice genome contains two homologous UGPase genes, OsUgp1 and OsUgp2. We present evidence that both OsUgp1 and OsUgp2 are ubiquitously expressed throughout rice development, and that OsUgp1 is expressed at much higher levels than OsUgp2. In accordance with the gene expression patterns, the UGPase isoform derived from the OsUgp1 gene predominated in various rice tissues and exhibited qualitative variations (position shifts and presence/absence) between rice varieties B5 and Taichung native 1 (TN1). Our results demonstrate that these qualitative variations are attributable to a single amino acid substitution of Asp-462 in B5 by His in TN1, corresponding to the allelic difference in the OsUgp1 gene between B5 and TN1.
Physiologia Plantarum 02/2007; 129(4):725 - 736. · 3.11 Impact Factor
