CD44 Upregulation in E-Cadherin-Negative Esophageal Cancers Results in Cell Invasion

E-cadherin is frequently lost during epithelial-mesenchymal transition and the progression of epithelial tumorigenesis. We found a marker of epithelial-mesenchymal transition, CD44, upregulated in response to functional loss of E-cadherin in esophageal cell lines and cancer. Loss of E-cadherin expression correlates with increased expression of CD44 standard isoform. Using an organotypic reconstruct model, we show increased CD44 expression in areas of cell invasion is associated with MMP-9 at the leading edge. Moreover, Activin A increases cell invasion through CD44 upregulation after E-cadherin loss. Taken together, our results provide functional evidence of CD44 upregulation in esophageal cancer invasion

Foley Catheter versus Vaginal Misoprostol for Labour Induction

Objectives. To compare the efficacy and safety of intravaginal misoprostol with transcervical Foley catheter for labour induction. Material and Methods. One hundred and four women with term gestation, with Bishop score < 4, and with various indications for labour induction were randomly divided into two groups. In Group I, 25 μg of misoprostol tablet was placed intravaginally, 4 hourly up to maximum 6 doses. In Group II, Foley catheter 16F was placed through the internal os of the cervix under aseptic condition and then inflated with 50 cc of sterile saline. Statistical analysis was done using SPSS software. Results. The induction to delivery interval was 14.03 ± 7.61 hours versus 18.40 ± 8.02 hours (p<0.01). The rate of vaginal delivery was 76.7% versus 56.8% in misoprostol and transcervical Foley catheter group, respectively. Uterine hyperstimulation was more common with misoprostol. Neonatal outcome was similar in both the groups. Conclusion. Intravaginal misoprostol is associated with a shorter induction to delivery interval as compared to Foley’s catheter and it increases the rate of vaginal delivery in cases of unripe cervix at term. Transcervical Foley catheter is associated with a lower incidence of uterine hyperstimulation during labour

Inverse correlation of E-cadherin and CD44 expression in primary human esophageal tumors.

<p>IHC with anti-CD44 antibody shows increased CD44 expression during the progression from normal (A) to carcinoma <i>in situ,</i> CIS (B), and tumor (C). Antibody against E-cadherin and CD44 show expression of E-cadherin (D) and in the absence of CD44 (E) in the normal epithelium. In EAC tissues with retained E-cadherin expression (F, dashed black line) the signal for CD44 is low (G). (H) Loss of E-cadherin is associated with an intense signal for CD44 (I). Scale bar is 50 micron.</p

CD44 co-localizes with MMP-9 in areas of invasion and is upregulated by Activin A.

<p>(A) For <i>in situ</i> zymography, areas of MMP activity are highlighted by a positive fluorescein signal on frozen sections of Ecad, EC and ECdnT organotypic cultures. (B) Zymography using organotypic culture conditioned medium collected from Ecad, EC and ECdnT cells illustrates increased secretion of MMP-2 and MMP-9. (C) Double immunofluorescence staining of Ecad, EC and ECdnT shows MMP-9 (red) colocalization with CD44 (green) in invasive cells. Scale bar is 50 micron. (D) Stimulation with Activin A induces enhanced invasion of ECdnT and TE-11 cells in invasion assays. Comparison between groups was done by Man and Whitney non- parametrical test, * p<0.05, **p<0.001. (E) Western Blot of cell lysates from TE-11 transfected with AllStars negative non-silencing siRNA cells (ctrl), and TE-11 cells transfected with siRNA against E-cadherin (si1, si2) demonstrates upregulation of CD44 after stimulation with Activin A.</p

CD44 expression is increased in areas of invasion after E-cadherin loss.

<p>Immunohistochemistry of paraffin sections with anti-E-cadherin antibody (A), anti-TGFβRII (B) and anti-CD44 (C) shows CD44–positive cells in EC and ECdnT cells invading into the underlying collagen/matrigel matrix (arrows) that are negative for E-cadherin and TGFβRII. Immunohistochemical staining for the EMT markers S100A4 (D), vimentin (E) and αSMA (F) shows increased positive signal in invading cells. Scale bar is 50 micron.</p

Expression of CD44, TGFβRII, vimentin and E-cadherin in cancer cell lines.

<p>(A) Western Blot analysis of esophageal squamous carcinoma cell lines (TE-1 -7, -8, -11, and -12), esophageal adenocarcinoma cell lines (FLO-1, OE33, SK-GT-4) and head and neck cancer cell lines (JHU-012, JHU-013) show that expression of E-cadherin and TGFβRII is associated with low levels of CD44, while loss of E-cadherin and TGFβRII correlates with up-regulation of CD44 and the EMT marker vimentin. (B) Restoration of E-cadherin, Ecad, expression by retroviral transfection of TE-8 and FLO-1 cells compared to vector control (neo) demonstrates an overall decrease in CD44 expression along with a switch to increased CD44v over CD44s (CD44v: CD44variant, CD44s: CD44 standard).</p