Cripto-1 enhances migration and branching morphogenesis of mouse mammary epithelial cells

Exp Cell Res. 2001 May 15;266(1):95-105. doi: 10.1006/excr.2001.5195.

Abstract

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.

MeSH terms

  • Animals
  • Biological Assay / methods
  • 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
  • Culture Media, Serum-Free / pharmacology
  • Epidermal Growth Factor*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology
  • Glycogen Synthase Kinase 3
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • 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

Substances

  • Culture Media, Serum-Free
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Tdgf1 protein, mouse
  • Epidermal Growth Factor
  • Phosphatidylinositol 3-Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Glycogen Synthase Kinase 3