Journal of the American College of Surgeons
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Tumor cells undergoing epithelial-mesenchymal transition (EMT) develop cellular properties leading to stroma invasion and intravasation. We have previously shown in a xenograft breast cancer model that blocking osteopontin (OPN), a secreted phosphoprotein, decreases EMT. This study examines OPN's role in EMT initiation through its regulation of EMT transcription factors (TFs) Snail, Slug, and Twist. OPN's role in Twist activation is examined through immunoprecipitation and Western blot. ⋯ This study shows that OPN is critical in EMT initiation through activation of Twist via serine phosphorylation. These unique observations indicate that OPN APT can serve a clinical role as a novel therapeutic agent by diminishing breast cancer oncogenesis.
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Orthotopic mouse models of human gastric cancer represent an important in vivo tool for testing chemotherapeutic agents and for studying intraluminal factors. Currently, orthotopic mouse models of gastric cancer require an operative procedure involving either injection or implantation of tumor cells in stomach layers. The resultant tumor does not grow from the stomach's mucosal surface, so it does not mimic the human disease process. ⋯ Our model is easy to create and overcomes the limitations of the existing models, as the tumor arises from the stomach's mucosal layer and mimics the human disease in terms of morphology and biologic behavior. This is the first report of a true orthotopic gastric cancer murine model. This model opens new doors for additional studies that were not possible earlier.