Cripto-1 Enhances Migration and Branching Morphogenesis of Mouse Mammary Epithelial Cells

• Published in: Experimental cell research 2001-05, Vol.266 (1), p.95-105
• Main Authors: Wechselberger, Christian, Ebert, Andreas D., Bianco, Caterina, Khan, Nadia I., Sun, Youping, Wallace-Jones, Brenda, Montesano, Roberto, Salomon, David S.
• Format: Article
• Language: English
• Subjects: Animals; Biological Assay - methods; branching; Breast - drug effects; Breast - growth & development; Breast - metabolism; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Division - drug effects; Cell Division - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cell Size - drug effects; Cell Size - physiology; Cells, Cultured - drug effects; Cells, Cultured - metabolism; cripto-1; Culture Media, Serum-Free - pharmacology; Epidermal Growth Factor; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; epithelial–mesenchymal transition; Female; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - physiology; Glycogen Synthase Kinase 3; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; migration; Mitogen-Activated Protein Kinases - drug effects; Mitogen-Activated Protein Kinases - metabolism; mouse mammary epithelial cells; Neoplasm Metastasis - physiopathology; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasm Proteins - pharmacology; Phosphatidylinositol 3-Kinases - drug effects; Phosphatidylinositol 3-Kinases - metabolism; RNA, Messenger - metabolism; Transgenes - drug effects; Transgenes - physiology
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1006/excr.2001.5195

Cripto-1 is an EGF-CFC protein that performs an important role during early vertebrate development and is overexpressed in several types of human cancer. In the present study mouse EpH4, NMuMG, and TAC-2 mammary epithelial cells that are negative for endogenous cripto-1 expression were transfected with the murine cripto-1 cDNA. Cripto-1-transfected cell lines exhibited functional and physiological differences from the original cell lines including enhanced anchorage-independent growth in soft agar (EpH4 cells), growth in serum-free medium, increased proliferation, and formation of branching, duct-like structures when grown in a three-dimensional collagen type I matrix. Furthermore, cripto-1-expressing cell lines showed elevated migration in vitro in Boyden chamber and wound-healing assays. These results indicate that cripto-1 can function through an autocrine pathway that enables mammary epithelial cells to undergo an epithelial to mesenchymal transition.