Variation in cadherins and catenins expression is linked to both proliferation and transformation of Rhabdomyosarcoma

Cadherins are a family of transmembrane glycoproteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion and play a crucial role in cell differentiation. E-cadherin-mediated cell-cell adhesion is lost during the development of most epithelial cancers. This study examines cadherin-dependent adhesion in cell lines derived from rhabdomyosarcoma (RMS), a highly malignant soft-tissue tumor committed to the myogenic lineage, but arrested prior to terminal differentiation. We analysed the expression of cadherins and associated catenins at the mRNA and protein levels as well as their localization in nine RMS-derived cell lines relative to normal myoblasts. We show a decrease in the expression of cadherins and catenins in all RMS-derived cell lines compared to control cells. This decrease in the expression of N- and M-cadherin was confirmed in RMS biopsies. In contrast, R-cadherin is found expressed in RMS, whereas it is normally absent in normal myoblasts. We show that a decrease of R-cadherin expression using RNA interference inhibits cell proliferation of the RD cell line. In addition to their diminished expression, cadherins and catenins do not localize to intercellular contacts in embryonal RMS (ERMS), whereas specific persistent localization is seen in alveolar RMS (ARMS)-derived cell lines. Thus, RMS exhibit defects in the expression of molecules of the cadherin family. Defects in the localization of these adhesion molecules at the sites of cell-cell contact are specifically observed in the ERMS subtype. In addition, our data suggest that R-cadherin is a specific diagnostic marker for RMS and is also an important factor of RMS cell proliferation.     

The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation

Epithelial cell adhesion molecule (EpCAM) is a membrane glycoprotein expressed on adenomatous and simple epithelia, where it is involved in homophilic adhesion at the basolateral membrane. Carcinomas strongly overexpress EpCAM through an, as yet, unknown mechanism. Interestingly, otherwise EpCAM-negative squamous epithelia are seen to express EpCAM concomitant with their transformation and de-differentiation. The amount of EpCAM and the number of expressing cells both increase with the grade of dysplasia. Despite an important amount of data correlating the expression of EpCAM with cellular proliferation and de-differentiation, such as the coexpression with Ki-67, a marker for proliferation, it is unknown whether EpCAM may directly contribute to carcinogenesis. Here, we show that EpCAM has a direct impact on cell cycle and proliferation, and the ability to rapidly upregulate the proto-oncogene c-myc and cyclin A/E. Human epithelial 293 cells as well as murine NIH3T3 fibroblasts expressing EpCAM had a decreased requirement for growth factors, enhanced metabolic activity and colony formation capacity. Importantly, the inhibition of EpCAM expression with antisense mRNA led to a strong decrease in proliferation and metabolism in human carcinoma cells. Moreover, domain swapping experiments demonstrated that the intracellular part of EpCAM is necessary and sufficient to transduce the effects described. Thus, the data presented here highlight the role of EpCAM, demonstrating for the first time a direct link to cell cycle and proliferation.     

Liver involvement revealing systemic mastocytosis: report of two cases

Systemic mastocytosis is a disease defined by an abnormal infiltration of mast cells involving several extra-cutaneous organs. Hepatic involvement is frequent, however it rarely reveals the disease. We report two cases of systemic mastocytosis revealed by hepatic symptoms: liver failure in one case and jaundice in the second case. The diagnosis is often difficult. Mast cell tissular infiltration can be identified on paraffin sections by tryptase or CD117 (c-kit) immuno-staining.     

Endoscopic management of pancreatic fistula after pancreatic and other abdominal surgery

Post-operative pancreatic fistulae represent a challenge for all the actors in gastroenterology: for surgeons, because they want to prevent and treat conservatively this complication since re-operation is associated with high morbidity and mortality rates; for radiologists, because they have to provide the best staging and informations without any additional risk; and for endoscopists, because endoluminal treatment is emerging as a safe and effective procedure provided it is performed in highly experienced tertiary centres in the setting of a multidisciplinary approach. Herein, we review the definitions, the causes, the staging and the possible options to prevent or treat post-operative pancreatic fistulae. Special attention is paid to the endoscopic management of this complication: including the relief of ductal obstructions, the stenting of leakages and the drainage of bulging or non-bulging fluid collections. Practical problems and issues are clearly outlined as well as the need for future improvements in staging and management of the patients having such complications.