Invasion Suppressor Role of E-Cadherin in Epithelial Cancer Cell Lines

ABSTRACT

BACKGROUND: The generation of the invasiveness in transfromed cells represents an essential step of tumor progression. The primary cause of the scattering of the cells in invasive carcinoma is a loss of the integrity of the intercellular adherens junction often involving loss of a functional cell-cell adhesion molecule E-cadherin. Therefore, the perturbation of E-cadherin function causes diaggregation of tumor cells and may promote the invasion and metastases. OBJECTIVE: The reduction in E-cadherin activity seems to correlate with the infiltrative ability of tumor cells. The purpose of this study was to compare the E-cadherin expression among different cell lines which were normal to undifferentiated and to check the virtual relationaship between E-cadherin and invasiveness. METHODS: We used 5 cell lines, HaCaT, A431, C3, SiHa and HeLa cell. To check the expression patterns and amounts of E-cadherin in each cell line, immunofluorescence staining, Western blot anlysis and Northern blot analysis were done. An in vitro invasion assay using the collagen gel and MRC-5 fibroblast under the influence of HECD-1 antibody which block the E-cadherin function was done to measure the invasiveness of tumor cells. Collagenase activity in culture supernatants of each cell were analyzed by zymography. RESULTS: Immunofluorescence staining revealed a homogenously well preserved pattern in HaCat, A431, C3 cells. SiHa cells showed patch distribution but HeLa cells did not express the E-cadherin. Western blot analysis and Northern blot results largely corresponded with the immunofluorescence results. The in vitro invasion assay revealed invasion into the collagen matrix of the HeLa cells. When HECD-1 antibody was added to the medium, other cells showed partially disrupted stratification. The collagenolytic activity at 72 kDa sixe was detected in the HeLa cell line only. CONCLUSION: There is an inverse relationship between E-cadherin expression and tumor invasion. Therefore, through their regulation of cell adhesion and motility, cadherin plays a crucial role in the suppression of tumor invasion and metastasis.