Cripto-1 enhances migration and branching morphogenesis of mouse mammary epithelial cells.
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.
Wechselberger
C
C
Laboratory of Tumor Immunology and Biology, Tumor Growth Factor Section, National Cancer Institute, National Institutes of Health, Building 10, Room 5B39, 10 Center Drive, Bethesda, Maryland 20892, USA.
Ebert
A D
AD
Bianco
C
C
Khan
N I
NI
Sun
Y
Y
Wallace-Jones
B
B
Montesano
R
R
Salomon
D S
DS
D000818:Animals; D001681:Biological Assay / Q000379:methods; D001940:Breast / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D048429:Cell Size / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004815:Epidermal Growth Factor; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D038362:Glycogen Synthase Kinase 3; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019076:Transgenes / Q000187:drug effects / Q000502:physiology
D016895:Culture Media, Serum-Free; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C489450:Tdgf1 protein, mouse; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3