CD44v4 Is a Major E-Selectin Ligand that Mediates Breast Cancer Cell Transendothelial Migration

BACKGROUND: Endothelial E-selectin has been shown to play a pivotal role in mediating cell-cell interactions between breast cancer cells and endothelial monolayers during tumor cell metastasis. However, the counterreceptor for E-selectin and its role in mediating breast cancer cell transendothelial migration remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: By assessing migration of various breast cancer cells across TNF-alpha pre-activated human umbilical vein endothelial cells (HUVECs), we found that breast cancer cells migrated across HUVEC monolayers differentially and that transmigration was E-selectin dependent. Cell surface labeling with the E-selectin extracellular domain/Fc chimera (exE-selectin/Fc) showed that the transmigration capacity of breast cancer cells was correlated to both the expression level and localization pattern of E-selectin binding protein(s) on the tumor cell surface. The exE-selectin/Fc strongly bound to metastatic MDA-MB-231, MDA-MB-435 and MDA-MB-468 cells, but not non-metastatic MCF-7 and T47D cells. Binding of exE-selectin/Fc was abolished by removal of tumor cell surface sialyl lewis x (sLe(x)) moieties. Employing an exE-selectin/Fc affinity column, we further purified the counterreceptor of E-selectin from metastatic breast cancer cells. The N-terminal protein sequence and cDNA sequence identified this E-selectin ligand as a approximately 170 kD human CD44 variant 4 (CD44v4). Purified CD44v4 showed a high affinity for E-selectin via sLe(x) moieties and, as expected, MDA-MB-231 cell adhesion to and migration across HUVEC monolayers were significantly reduced by down-regulation of tumor cell CD44v4 via CD44v4-specific siRNA. CONCLUSIONS/SIGNIFICANCE: We demonstrated, for the first time, that breast cancer cell CD44v4 is a major E-selectin ligand in facilitating tumor cell migration across endothelial monolayers. This finding offers new insights into the molecular basis of E-selectin-dependent adhesive interactions that mediate breast cancer cell transendothelial metastasis

Occiput posterior position and intrapartum sonography

The occiput posterior position is reported to be the most common of all malpositions, and it may present as either straight (OP), left (LOP), or right (ROP). Diagnosis of OP position can be made at different times: during the third trimester, prior to the onset of labor, during the first stage of labor, while the fetus is transiting in the birth canal, and at birth. The time of diagnosis, though, is of different clinical significance, moving or not to a very specific management. Manual diagnosis of occiput posterior position either with abdominal palpation or vaginal examination is very subjective, prone to mistake, operator dependent, and made more difficult by caput and molding. Intrapartum ultrasonography has become a very reliable tool to hell the clinician to make a true diagnosis of malposition. The ultrasound probe may be used with different approach: transabdominal, suprapubical, transperineal, and transvaginal. The correct diagnosis of fetal head position as occiput posterior is imperative to be obtained in the management of any dystocia that may occur in the different stages of labor. Its knowledge will help the clinician to make the right decision at the right time, with the ultimate goal to reduce maternal and neonatal morbidity

Hydroformylation in Aqueous Biphasic Media Assisted by Molecular Receptors

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