EGCG has inhibitory effect on a variety of cancers by inducing apoptosis and cell cycle arrest or inhibiting angiogenesis and metastasis. EGCG has been found to induce apoptosis in salivary gland carcinoma cells. But the potential anti-invasive effect of EGCG in salivary gland cancer has not been studied yet. The aim of this study is to evaluate the effect of EGCG on salivary gland adenocarcinoma SGT cell adhesion and migration to Type I collagen treatment. Western blot, adhesion and migration assay were performed to evaluate the impacts of EGCG on the expression of MMP-2/-9 and its upstream signaling molecules after treatment of type I collagen. SGT cell adhesion to type I collagen is significantly suppressed by EGCG. EGCG decreased expression of β1 integrin, phosphorylation of FAK, MMP-2/-9 compared with type I collagen treatment. In addition, EGCG inhibited the migration of SGT cells treated with type I collagen. These results suggest that EGCG could effectively inhibit the invasion and migration of human SGT cells by downregulating the expression of β1 integrin and MMP-2/-9 and phosphorylation of FAK, Akt, and Erk. Adhesion and migration to type I collagen of SGT cells can be influenced through EGCG.
Cancer cells are often found in an ischemic condition due to the rapid outgrowth of their vascular supply, and these cells are expected to develop an increased potential for local invasive growth. Since the first steps are characterized by increased motility and invasiveness, expression of molecules involved in cellular adhesion to extracellular matrix (ECM) is increased in the process of cancer cell invasion and metastasis. In this work we explored the molecular characteristics and its regulatory mechanism of hypoxic oral squamous cell carcinoma (OSCC) cells. Our experiment identified that hypoxia increases α5 integrin protein levels through phosphoinositide 3-kinase (PI3K)/Akt pathway in OSCC cells.
Human β- defensin-2 (hBD-2) is an antimicrobial peptide which is produced by epithelial cells after stimulation with microorganisms or inflammatory mediators. However, little is known as to whether the LPS and nicotine induces the expression of hBD-2 in periodontal l igament (PDL) cells. T he p urpose o f this s tudy was t o investigate t he r oles o f MAPKs pathway o f nicotine a nd L PS-induced hBD-2 expression in PDL cells. The maximal expression of hBD-2 was observed in nicotine 5 mM and LPS 1 μg/ml treated PDL cells. Nicotine and LPS induced the phosphorylation of p38, c-Jun N-terminal kinase 1 and 2 (JNK1/2), and extracellular signal-regulated kinases 1 and 2 (ERK1/2) MAPK. ERK1/2 inhibitor SB203580, p38 inhibitor PD98059, and JNK inhibitor SP600125, blocked the effects of nicotine and LPS on hBD-2 upregulation in PDL cells. These results collectively suggest that hBD-2 is up-regulated in nicotine and LPS-treated PDL cells through activation of p38, ERK and JNK MAPKs pathway. Our data regarding the up-regulation of hBD-2 may help us to understand the antimicrobial mechanism in periodontal disease
Oral squamous cell carcinoma (OSCC) is the most common cancer of oral cancers. Recent data suggest that chemokines could be essential players in carcinogenesis and that tumor cells express chemokine receptors and use chemokines to metastasize to the target organ in many malignancies in humans. The aim of this study was to test the hypothesis that expression of SNPs in chemokine, CXCL1 and CXCL2 correlates with oral squamous cell carcinomas in Korean population. The CXCL1 and CXCL2 genotypes were determined in 21 subjects with oral squamous cell carcinoma and 90 control subjects without oral squamous cell carcinoma. The genotypes were determined by direct sequencing. The genotype distribution and allele frequency within the OSCC patients were not significantly different from those of control subjects. But among OSCC subjects, there was significant difference of CXCL1 gene in the degree of nuclear aberration. These findings suggest that CXCL1 -442C/T polymorphism and CXCL2 -264T/C polymorphism are not related to the development of OSCC but polymorphism of CXCL1 gene might have a relation with progression of OSCC in Korean population.
Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. It is biphasic and is characterized by an admixture of epithelial and spindle-shaped myoepithelial cells in a variable background stroma. Epithelial-myoepithelial carcinoma (EMC) is a malignant biphasic salivary gland tumor typically composed of clear myoepithelial cells that surround epithelial-lined ducts resembling intercalated ducts. The differential diagnosis between the two tumor may be occasionally encountered because of the shared histophatologic feature. And then, it would be more reliable to differentiate the tumors based on biological behavior such as the expression of distinct intermediate filaments such as cytokeratin, invasiveness- related molecules, and the growth factor receptor to aberrantly facilitate the tumor growth, and the growth fraction of tumors. Therefore, from the 10 cases of PA and 6 cases of EMC, we immunohistochemically examined the differential expression of the cytokine 7 and 14, matrix metalloproteinase-9, C-KIT, and Ki-67 between the two tumor. At the results, there were significant differences of CK7 expression in non-luminal cells (P = 0.000) and CK14 expression in luminal and non-luminal cells of the both tumors (P = 0.025 and P = 0.000, respectively). In the comparison of the biologic behavior, a significantly increased expression of MMP-9, C-KIT and Ki-67 was found in the cases of EMC when compared to those of PA (P = 0.043, P = 0.011, and P = 0.000, respectively). In conclusion, the differences of CK expression in luminal and non-luminal cells between PA and EMC seem to reflect the difference of the origin and the level of the maturation of the tumor cell. Increased expression of MMP-9, C-KIT, and Ki-67 in EMC may represent more aggressive biologic behavior of the tumor compared with benign salivary tumor such as PA. Our results may be helpful to understand the histiogenesis of the two tumors and the difference of biologic behavior and to differentiate them when the limited specimen was submitted. Further study of many more cases of EMC is needed to validate the usefulness of these molecules as the diagnostic aid.
Human pituitary tumor transforming gene 1 (PTTG1), which is a newly identified proto-oncogene, is highly expressed in normal pituitary tissues containing proliferating cells and in several cancers. Also, PTTG1 has been known as a securin to involve in the regulation of c ell-cycle and in t he p rogression o f tumor. B u t the effect o f PTTG1 in o ral squamous cell carcinoma (oral SCC) h as not b een studied yet. The objective of this study is to analyze the expression of PTTG1 in oral SCC cell lines (YD-10B and YD-15) and to evaluate the effect of PTTG1 on oral SCC cell lines for the migration effect by PTTG1 siRNA treatment. Western blot, migration assay, and zymography were performed to evaluate the effects of PTTG1 on the expression of MMP-2/-9 and migration activity after PTTG1 siRNA treatment. PTTG1 was expressed in oral SCC cells lines, otherwise, significantly decreased after PTTG1 siRNA treatment. There is no difference in expression of MMP-2 regardless of PTTG1 siRNA treatment. However, the enzyme activity of MMP-9 was significantly decreased. In addition, the migration activities of oral SCC cells were significantly decreased after PTTG1 siRNA treatment (p<0.001). These results suggested that the down-regulated PTTG1 could inhibit the migration of human oral SCC cells through the low MMP-9 expressions. Therefore, these findings provide a useful guideline for the migration mechanism of oral SCC depend on PTTG1 expression.
This report describes a case of odontogenic cyst with keratinization and dysplastic change of lining epithelium, which showed the manifestation of inflammatory radicular cyst, clinically. A 28-year-old man complained of dull pain in the right mandibular molar region. Radiographically a well-defined oval cystic lesion with non-vital teeth, a common finding in radicular cyst, was observed. Microscopically, the lining epithelium of the cyst demonstrated both keratinization and severe epithelial dysplasia. Atypical findings such as hyperchromatic nuclei, increase of N/C ratio and drop shaped rege ridge were observed in the lining epithelium. However, definite invasion into fibrous connective tissue was not found. Immunohistochemically, the dysplastic lining epithelium was highly positive for proliferative marker, Ki-67. Based on the dysplastic changes of lining epithelium, this periapical lesion would be considered to be signs of malignant change. From this case, we conclude that definitive diagnosis by microscopical examination should be made, even if the periapical lesion would be clinically considered as inflammatory radicular cyst.