The over-expression of α1,2-FT cDNA results in the elevation of Lewis y content on some surface receptors, which might alter the comformation of the receptors, then promoting the signaling of the receptor and finally

stimulating the proliferation of ovarian cancer cells. Our studies have found that the total amount of surface Lewis y as well as the Lewis y content on some surface receptors were all increased, and Lewis y expression on EGFR was very high on α1,2-FT-transfected cells (in press). Cross-talk between the PI3K/Akt and the Raf/MEK/MAPK signaling pathways has been implied in human various malignant tumors, with BAY 63-2521 concentration some research stating that PI3K activity is essential for induction

of Raf/MEK/MAPK activity [41, 42]. Additional studies R406 cost suggest that the PI3K/Akt pathway enhances and/or synergizes with Raf/MEK/MAPK signaling to provide a more robust survival signal [43]. We speculate whether such cross-talk between the two pathways also exists in Lewis y-overexpressing ovarian cancer cells, and whether Lewis y is the key point for triggering or regulating this cross-talk, the detailed mechanism requires further study. The changes in glycosyltransferase expression might affect the sugar chain heterogeneity and distribution, which may mask some tumor antigens, reduce the immunogenicity of tumor cells, and promote tumor cells immune evasion. It has been confirmed that under normal circumstances, T lymphocytes do not recognize Lewis y antigen [44]. This allows the evasion of tumor selleck chemicals cells from the recognition and killing by the human immune system, in order to easily enter the lymph nodes to form metastasis. Other studies found a novel function for soluble Lewis y, that is inducing cytokine release, such as interleukin-6 (IL-6), through the Janus kinase 2 (JAK2) pathway [45, 16]. We speculate that except for proliferation, Lewis y could also induce tumor cells immune evasion through activating PI3K/Akt signaling pathway, the detailed mechanism

is being studied. Lewis y may participate in natural humoral immune response, antibodies are ideally suited for selleck inhibitor eradicating pathogens from bloodstream and early tissue invasion. With regard to cancer cells, passively administered and vaccine induced antibodies have accomplished this concept, limiting tumor cells and systemic or intraperitoneal micrometastases in a variety of preclinical models. Many protocols developing anti-Lewis y vaccines have been performed [46, 47]. In summary, we showed that increased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells. Inhibition of Lewis y expression may provide a new therapeutic approach for Lewis y positive ovarian cancer.