Neovascularization plays a critical role in cancer metastasis. However, the molecular mechanism regulating the neovascularization in oral squamous cell carcinoma (OSCC) is poorly understood. Placental growth factor (PLGF) has been known to regulate pathological angiogenesis and has been recently shown to regulate matrix metalloproteinases (MMPs) for extracellular matrix degradation during neovascularization. Here we aimed to examine whether PLGF may regulate MMPs in the metastasis of OSCC. We found that PLGF and MMP9 levels strongly correlated in OSCC in the patients, both increased in the OSCC from the patients with metastasis of the primary OSCC. Thus, we used several human OSCC cell lines to examine the relationship between PLGF and MMP9. We found that overexpression of PLGF in OSCC cells increased expression of MMP9, while inhibition of PLGF in OSCC cells decreased expression of MMP9. However, adaptation of MMP9 levels in OSCC cells did not affect the levels of PLGF. These data suggest that PLGF may regulate MMP9 in OSCC cells, but not vice versa. Moreover, inhibition of ERK1/2, but not inhibition of PI3k or JNK pathways, substantially abolished the effect of PLGF on MMP9, suggesting that PLGF may increase expression of MMP9 via ERK/MAPK signaling pathway. Thus, our data demonstrate that PLGF-induced cancer neovascularization may be partially mediated through its effect on MMP9 activation in OSCC.

BackgroundTransgelin is supposed to be a tumor suppression gene and it is down-regulated in a variety of human cancers. However, the role of transgelin in different cancers is still very controversial. In addition, currently little information is available the relationship between transgelin and Oral Squamous Cell Carcinoma (OSCC).Material/MethodsWestern Blotting was performed to test the transgelin protein expression level in OSCC tissues and adjacent normal tissues. Real-time PCR was used to examine the expression level of transgelin mRNA in tissue, serum and saliva of OSCC patients and negative controls. The correlation between tissue and salivary transgelin mRNA expression level with a variety of clinical parameters was further studied.ResultsTransgelin protein expression was increased in OSCC patients compared with healthy individuals. Similarly, the expression level of both tissue and salivary transgelin mRNA were increased significantly in patients with OSCC in comparison with normal controls. However, little difference of serum transgelin mRNA expression was found between the OSCC patients and healthy controls. In addition, overexpression of tissue or salivary transgelin was closely associated with various clinical parameters including poorer overall survival. Furthermore, our results showed that tissue and salivary transgelin mRNA were independent prognosis factors for OSCC.ConclusionsThe expressions level of tissue mRNA and protein were increased in OSCC patients. Both tissue and salivary transgelin mRNA were closely correlated with various important clinicopathological parameters and were independent prognosis factors for OSCC, indicating they might serve promising biomarkers for OSCC.

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OBJECTIVE To assess the significance of sentinel lymph node biopsy (SLNB), serial section and cytokeratin immunohistochemical staining in the diagnosis and staging of Stage-cN0 oral squamous cell carcinoma (OSCC). METHODS A blue stain, 99mTc-dextran SPECT lymphoscintigrapgy and intraoperative γ-ray probes were used to examine the sentinel nodes in 31 cases with Stage-cN0 oral cancer. The H&E staining and a cytokeratin AE1/ AE3 immunohistochemistry (IHC) assessment, with serial sections, were conducted to provide results obtained from a routine pathological examination of lymph nodes. The value of the routine pathological examination of the sentinel lymph node (SLN), serial sections and IHC determination for cervical lymph node metastasis of Stage-cN0 OSCC was appraised. RESULTS A total of 45, 55 and 51 SLNs were examined in 25 (80%), 31 (100%) and 30 (96.5%) of the cases, by using the blue stain, γ-ray probes, and SPECT lymphoscintigraphy, respectively. The average SLNs found in each case of the groups was 1.4 (1 to 3) and there were 1,302 non-NSLNs. Six positive SLN metastases were detected by routine pathological examination, among which 1 case was found to be an accompanied positive metastasis of non-SLN. One positive SLN metastasis was found after examination of serial sections plus routine H&E staining and 2 were detected using serial sections plus AE3 immunohistochemical staining methods. No positive NSLNs were found in the study. CONCLUSION In order to make more progress in accurate SLNB diagnosis, serial sections and IHC (AE1/AE3) methods can be used for examination of the micrometastases which are difficult to identify by routine pathological sections and H&E staining.