Sialic Acid Expressed On The Membrane Of Tumor Cell Line HeLa Influences Gap Junction Intercellular Communication

Gap junction intercellular communication (GJIC) is a pathway of direct cell to cell communication. It is accepted that cells of most invertebrate and vertebrate tissues can communicate with their neighbors via this pathway. Gap junction channels are responsible for direct intercellular transfer of small molecules without through intercellular substance. This type of intercellular communication is known to be essential for various physiological and pathophysiological functions, such as cell growth, proliferation and differentiation, tissue homeostasis, cell adhesion and movement, the propagation of action potentials, tumorigenicity, wound healing, etc. In cancer, loss of these types of cell to cell interactions has been shown to facilitate tumorigenesis. Indeed, many human tumor lines demonstrate deficient GJIC and/or loss or low of connexin expression or aberrant expression of connexin. Restoration of GJIC function by endogenous or exogenous connexin expression is correlated with increased cell growth control both in vitro and in vivo. These studies strongly suggest that connexins and GJIC serve a tumor suppressor role. It is the possible that connexins will be potential anti-oncogenic targets for chemoprevention and/or chemotherapy.Sialic acid is an important part of glycoprotein and glycolipid on the cellular membrane. Its metabolism plays a role in tumor proliferation, invasion and metastasis. Sialic acid on tumor cell surface is markedly higher than normal cells. For example sialic acid is expressed in cervix uteri cancer cells but not normal cervix uteri cells. It is highly expressed in patients'cervix uteri cancer tissues which are in low cell differentiation and later clinical stage.Many articles reported that GJIC is lower in tumor cells than normal. One possible reason is low expression level of Cx43, the other is that Cx43 can't form correct and complete channels which is related with mass anormaly glycons on the tumor cell surface. It's thought that the mass anormal glycons hinder the formation of GJIC channels. Many searches confirm that suppressing glycosylation by tunicamycin makes for opening of GJIC channels. We suppose that the anormal increase of sialic acid on the tumor cell surface would influence GJIC by this way too. Due to the lack of potential glycosylation sites in their exacellular loops, Cx43 is unlikely to be glycosylated. Therefore, a reduction of carbohydrates from cell surface proteins other than Cx43 is a more likely cause for the observed increase in communication.This article tries to study and research whether and how mass anormal sialic acid on tumor cell surface inhibits GJIC and its molecular mechanism, using modern molecular biology technique, cytobiology technique, varied laser biology technique such as LSM and FCM.GJIC of HeLa which is detected by both SLDT and FRAP is increased after removal ofα2-3 andα2-6 sialic acid by neuraminidase. The expression and phosphorylation of Cx43 are not obviously changed after treatment, but the distribution of Cx43 is changed and the quantity of Cx43 in the gap junctional plaques is increased. This maybe makes GJIC increased. This change happens partly because the quantity of Zo-1 binding to Cx43 is increased after removal of sialic acid, and it's reported that Zo-1 can mediat delivery of Cx43 from lipid raft domain to gap junctional plaques. So it may be one of the reasons that make GJIC increased.The study of this article is helpful to elucidate the biological function of sialic acid on tumor cell surface, and to provide theory on drug research and development arming at tumor GJIC and anormal glycons.