Previous studies implicated the role of Notch4 signaling in cell fate, such as differentiation of progenitor cells and tumorgenesis, and that activation of Notch4 gene inhibited mammary epithelial cell differentiation and promoted tumor formation.29, 30, 31 This has prompted us to test whether differentiating CLP-Int-αvβ3pos cells will inhibit Notch4 expression and its downstream signaling in the 3D BME system. This evidence concerns the gene NOTCH4 and neoplasm.