Characterization of integrin and anchorage dependence in mammary epithelial cells following c-erbB2-induced epithelial-mesenchymal transition.
Signalling from the proto-oncogene c-erbB2 in mammary epithelial cells has earlier been shown to result in epithelial-mesenchymal transition (EMT) giving rise to fibroblast-like cells, and acquisition of anchorage-independent growth (AIG) usually determined by growth capacity in soft agar. In this study, we have analysed AIG associated with c-erbB2-induced EMT in a human mammary epithelial cell line. Intriguingly, cells capable of growth in soft agar were shown to be dependent on the function of beta(1) integrin extracellular matrix receptors for growth in collagen. We therefore tested the hypothesis that apparent AIG was due to deposition of extracellular matrix in the agar. Although the fibroblastic cells had strongly upregulated expression of the fibronectin receptor subunit integrin alpha(5) andabundant fibronectin fibrils, these properties did not have a positive correlation with AIG. Furthermore, antibody blocking of integrin alpha(5) and beta(1) failed to inhibit AIG. These results indicate that the anchorage-independent cells are not dependent on connection to extracellular matrix, but instead may be subject to a growth-inhibitory effect from the collagen in the absence of integrin signalling. This notion was supported by the finding that integrin blocking of the fibroblastic cells in fibrin was without effect on proliferation.
Jenndahl
Lachmi E
LE
Department of Medical Biochemistry, University of Goteborg, Sweden.
Taylor-Papadimitriou
Joyce
J
Baeckstrom
Dan
D
D001943:Breast Neoplasms / Q000503:physiopathology*; D002450:Cell Communication; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology; D005109:Extracellular Matrix; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D016023:Integrins; D042361:Mammary Glands, Human / Q000166:cytology*; D008648:Mesoderm; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D017469:Receptors, Fibronectin / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction; D015854:Up-Regulation
D016023:Integrins; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D017469:Receptors, Fibronectin; C000715470:MAS1 protein, human