The coxsackievirus and adenovirus receptor (CAR) mediates viral attachment and infection, but its physiologic functions have not been described. In nonpolarized cells, CAR localized to homotypic intercellular contacts, mediated homotypic cell aggregation, and recruited the tight junction protein ZO-1 to sites of cell-cell contact. In polarized epithelial cells, CAR and ZO-1 colocalized to tight junctions and could be coprecipitated from cell lysates. CAR expression led to reduced passage of macromolecules and ions across cell monolayers, and soluble CAR inhibited the formation of functional tight junctions. Virus entry into polarized epithelium required disruption of tight junctions. These results indicate that CAR is a component of the tight junction and of the functional barrier to paracellular solute movement. Sequestration of CAR in tight junctions may limit virus infection across epithelial surfaces.G roup B coxsackieviruses and a number of adenovirus serotypes initiate infection by binding to the coxsackievirus and adenovirus receptor (CAR) (1-3). CAR is a 46-kDa integral membrane protein with a typical transmembrane region, a long cytoplasmic domain, and an extracellular region composed of two Ig-like domains (1, 2). Both adenovirus (4) and coxsackievirus (5) interact with the N-terminal domain. Homologs of human CAR have been characterized in mice (2, 6), rats, pigs, dogs (7), and zebrafish (8). The murine and human proteins are very similar (91% amino acid identity within the extracellular domain, 77% within the transmembrane domain, and 95% identity within the cytoplasmic domain). Variant isoforms of CAR, which differ only at the C terminus and which most likely result from alternative splicing, have been identified in mice (6), humans, and rats (7). Despite evidence of its evolutionary conservation in mammals and nonmammalian vertebrates, the function of CAR is not known.Tight junctions are continuous circumferential intercellular contacts at the apical poles of lateral cell membranes, appearing in electron micrographs as a series of discrete contacts between the plasma membranes of adjacent cells (9). Tight junctions form a barrier that regulates the paracellular transit of water, solutes, and immune cells across an epithelium (10), and are essential for establishing cell polarity by separating the apical and basolateral domains of polarized epithelial cells (11). ZO-1, the first tight junction protein identified (12, 13), is an intracellular peripheral membrane scaffolding protein important for tight junction structure and assembly. In the present study, we found that in polarized epithelial cells CAR is expressed at the tight junction, where it associates with ZO-1 and functions in the barrier to the movement of macromolecules and ions. Materials and MethodsCell Culture. T-84, CALU-3, and 16HBE14o-cells were grown in 10% CO 2 in a 1:1 mixture of DMEM and Ham's F-12 medium with 10% FCS. To establish polarized monolayers, 5 ϫ 10 5 cells per well were plated on 12-mm diameter polyester filters with a ...

Multiple and diverse cell adhesion molecules take part in intercellular and cell-extracellular matrix interactions of cancer. Cancer progression is a multi-step process in which some adhesion molecules play a pivotal role in the development of recurrent, invasive, and distant metastasis. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of cancer. Loss of intercellular adhesion and the desquamation of cells from the underlying lamina propria allows malignant cells to escape from their site of origin, degrade the extracellular matrix, acquire a more motile and invasion phenotype, and finally, invade and metastasize. In addition to participating in tumor invasiveness and metastasis, adhesion molecules regulate or significantly contribute to a variety of functions including signal transduction, cell growth, differentiation, site-specific gene expression, morphogenesis, immunologic function, cell motility, wound healing, and inflammation. Cell adhesion molecule (CAM), a diverse system of transmembrane glycoproteins has been identified that mediates the cell-cell and cell-extracellular matrix adhesion and also serves as the receptor for different kinds of virus. We summarize recent progress regarding the role of CAM, particularly, immunoglobulin-CAMs and cadherins in the progression of cancer and discuss the potential application of CAMs in the development of cancer therapy mainly on urogenital cancer.

Multiple and diverse cell adhesion molecules participate in intercellular and cell-extracellular matrix interactions of cancer. Cancer progression is a multistep process, in which some adhesion molecules have a pivotal role in the development of recurrent, invasive and distant metastasis. Recent data implicate some of these molecules in cell signaling and tumor suppression, which has important consequences for tumor growth.

PurposeAcute pyelonephritis (APN) with obstructive uropathy is not uncommon and often causes serious conditions including sepsis and septic shock. We assessed the risk factors for septic shock in patients with obstructive APN associated with upper urinary tract calculi.MethodsWe retrospectively studied 69 patients with obstructive APN associated with upper urinary tract calculi who were admitted to our hospital. Emergency drainage for decompression of the renal collecting system was performed for empirical treatment in cases of failure of initial treatment and for severe cases. We assessed the risk factors for septic shock by multivariate logistic regression analysis.ResultsOverall, 45 patients (65.2 %) underwent emergency drainage and 23 (33.3 %) patients showed septic shock. Poor performance status and the presence of diabetes mellitus (DM) in the septic shock group were more common than in the non-septic shock group (p = 0.012 and p = 0.011, respectively). The platelet count and serum albumin level in the septic shock group were significantly lower than in the non-septic shock group (p = 0.002 and p = 0.003, respectively). Positive rates of midstream urine culture and blood culture in the septic shock group were significantly higher than in the non-septic shock group (p = 0.022 and p = 0.001, respectively). Multivariate analysis showed that decreases in the platelet count (OR 5.43, p = 0.014) and serum albumin level (OR 5.88, p = 0.023) were independent risk factors for septic shock.ConclusionPatients with obstructive APN associated with upper urinary tract calculi who have decreases in platelet count and serum albumin level should be treated with caution against the development of septic shock.