engleski

The impact of Coxsackie and adenovirus receptor on cellular morphology, adhesion and proliferation

CAR (Coxsackie and Adenovirus Receptor) was first characterized as an adenoviral attachment site on the surface of epithelial cells, but its role in normal cell physiology is not yet resolved. It has been shown recently that CAR exhibits a tumor suppressive role which correlates with its down-regulation in malignant cells. Although most reports suggest its involvement in cell adhesion, a detailed insight into the mechanisms underlying the influence of CAR on cancer pathology is incomplete. The aim of our investigation is to explore if the increased expression of CAR has any influence on multiple processes of cellular metabolism ; such as cell adhesion, proliferation, migration, cell response to genotoxic agents and resistance to such compounds, as well as the influence on the induction of programmed cell death in cancer cells. Human rhabdomiosarcoma (RD) cells expressing low constitutive expression of CAR were transfected with plasmid harboring the CAR gene, yielding several clones with increasing levels of CAR. In the present study we examined the impact of CAR on cellular morphology, adhesion and proliferation. Our preliminary data show that increased expression of CAR induced slight changes in cell shape. However, the organization of actin and microtubule networks was similar in RD and CAR-overexpressing clones. Increased expression of CAR was clearly shown in CAR-overexpressing clones by flow cytometry and western blotting. The expression and cellular localization of cell-cell adhesion proteins: plakoglobin, beta-catenin, p120-catenin and desmoglein were similar in RD cells and RD-derived CAR-overexpressing clones. Regarding cell proliferation, two of the clones proliferate faster than the original RD cell line. In RD cells the rate of proliferation was dependent on initial cell density, while CAR-overexpressing clones do not show such strict dependence. Apart from regulating cytoskeleton organization, Rho GTPases are also involved in cell growth and cell cycle progression, cell adhesion, membrane trafficking, transcriptional regulation and apoptosis induction. Therefore, we examined the expression of RhoB in RD cells and CAR-overexpressing clones, but its constitutive expression was similar. Additional experimental studies, now in progress, are needed to explore the impact of CAR on complex processes involved in cancer pathology further.

coxsackie and adenovirus receptor; cadherins; catenins; RhoGTPases; cytoskeleton

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