Melanoma is one of the most deadly skin cancers. T-cadherin is an atypical member of the cadherin superfamily as it lacks the transmembrane and cytoplasmic domains and is anchored to cell membranes through glycosylphosphatidylinositol (GPI) anchors. T-cadherin downregulation is associated with a poorer prognosis in various carcinomas, such as lung, ovarian, cervical and prostate cancer, while in the majority of cancer cell lines, T-cadherin re-expression inhibits cell proliferation and invasiveness, increases susceptibility in apoptosis and reduces tumor growth in in vivo models. The functional relevance of T-cadherin gene expression in melanoma progression remains to be clarified. The present study was designed for this purpose. The T-cadherin gene was transfected into B16F10 melanoma cells to express T-cadherin in the cells which were originally deficient in T-cadherin expression. The proliferation, invasiveness, apoptosis and cell cycle of the transfected B16F10 melanoma cells were analyzed. The present study showed that the expression of T-cadherin in B16F10 melanoma cells markedly reduced cell proliferation and permeation through Matrigel-coated membranes, representing invasiveness. The percentage of early apoptotic cells and cells in the G2/M phase of the cell cycle was markedly increased compared with either parental B16F10 (without transfection) or empty pEGFP-N1 (without T-cadherin gene)-transfected B16F10 cells, suggesting G2/M arrest, with similarity between the parental and empty pEGFP-N1-transfected B16F10 cells. T-cadherin is important in melanoma progression and may be a possible target for therapy in melanoma and certain other types of cancer.
Keywords: T-cadherin; apoptosis; invasiveness; melanoma; proliferation.