Reduction of E-cadherin strongly relates to invasiveness and metastasis in vitro. To clarify CpG methylation around the promoter region of the E-cadherin gene in oral squamous cell carcinoma (SCC), we examined the DNA samples of various human SCC cell lines and primary oral SCC tissues by methylation-specific polymerase chain reaction (MSP). CpG methylation of the E-cadherin gene markedly correlated to the reduction of E-cadherin expression in human oral SCC cell lines. In primary oral SCC tissues, only 1 of 5 preserved E-cadherin-expressing tissues was methylated, whereas methylation was found in 17 (94.4%) of 18 E-cadherin-reduced tissues. Our results suggest that reduction of E-cadherin expression is associated with CpG methylation of the E-cadherin gene promoter. We recently established two cell lines with high and low metastatic potential, UM1 and UM2, from SCC primary tongue tissue of a patient. E-cadherin expression of high-metastatic UM1 was clearly lower than that of low-metastatic UM2, and MSP results showed CpG methylation in the UM1 but not the UM2 cell line. To investigate whether demethylation of CpG methylation of the E-cadherin gene could restore expression and function of E-cadherin, we treated UM1 with the demethylating agent 5-azacytidine (5-aza) and found that E-cadherin expression was indeed restored by demethylation. Moreover, in the demethylated UM1, invasion of the collagen gel was clearly suppressed compared with the untreated UM1. These results suggested that inactivation of E-cadherin expression resulted from CpG methylation of the gene promoter; a correlation between CpG methylation of the E-cadherin gene promoter and invasive potential was also suggested. © 2001 Wiley-Liss, Inc. Key words: E-cadherin; methylation; invasion and metastasis; human tongue SCCThe results of treatment for oral squamous cell carcinomas (SCCs) have been gradually improving due to advances in cancer therapies. However, this tumor is characterized by a high degree of local invasiveness to surrounding tissues as well as a high incidence of metastasis to cervical lymph nodes 1 and consequently causes local recurrence or distant organ metastases. Therefore, the prevention and control of such invasion and metastasis are important aspects of cancer therapies for oral SCCs.The pathogenesis of cancer metastasis consists of multiple sequential steps. [2][3][4][5][6] To accomplish the process of metastasis to other organs, cancer cells first detach from the primary tumor and invade the extracellular matrix. In this step, it has been widely accepted that the reduction of E-cadherin frequently causes cell release from the primary tumor. 7,8 E-cadherin, a 120 kD cell surface glycoprotein involved in calcium-dependent epithelial cell specific cell adhesion, is well known to mediate cell-cell communication and cell-cell adhesion between epithelial cells. 9,10 The reduction in E-cadherin, which acts as an invasion suppressor in human cancer, strongly relates to invasiveness and metastasis in vitro. 8,[11][12][13] In the clin...

Malignant tumors are composed of cells with different phenotypic properties and only certain cell subpopulations present metastatic potential. The establishment of cell lines with high or low metastatic potential is necessary to investigate the molecular mechanisms of the metastatic process. However, human oral squamous cell carcinoma (SCC) cell lines that are suitable for the above investigation are scarce. High and low metastatic cells were obtained from a primary lesion of a patient with tongue carcinoma who had not received any therapy. Two distinct cell lines were selected, UM1 with a scattered growth pattern and loose cell-cell adhesion, and UM2 with a colony-formed growth pattern and firm cell-cell adhesion. The expression of E-cadherin in UM1 was clearly lower than that in UM2. UM1 exhibited a higher motility, invasive and metastatic activity than UM2 in vivo and in vitro. A low invasive and a metastatic oral SCC cell line, useful to investigate invasion and metastasis mechanisms, have been established.

No abstract

These findings suggest that caspase-3 may mediate apoptosis induced by CDDP, and its induction could represent a novel approach to the effective treatment of malignant tumors.

No abstract