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Offterdinger, Martin; Schneider, Sonja M.; Grunt, Thomas W.

Heregulin and retinoids synergistically induce branching morphogenesis of breast cancer cells cultivated in 3D collagen gels

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  • Medientyp: E-Artikel
  • Titel: Heregulin and retinoids synergistically induce branching morphogenesis of breast cancer cells cultivated in 3D collagen gels
  • Beteiligte: Offterdinger, Martin; Schneider, Sonja M.; Grunt, Thomas W.
  • Erschienen: Wiley, 2003
  • Erschienen in: Journal of Cellular Physiology
  • Sprache: Englisch
  • DOI: 10.1002/jcp.10237
  • ISSN: 0021-9541; 1097-4652
  • Schlagwörter: Cell Biology ; Clinical Biochemistry ; Physiology
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>C‐erbB and retinoid receptor signaling control mammary epithelial cell proliferation, differentiation, and morphology. Here, we examined the morphogenetic activities of c‐erbB specific ligands such as heregulin and of retinoids on non‐malignant (primary, MTSV1‐7) and malignant (T47D, SKBR‐3) human mammary epithelial cells (HMEC) cultivated in 3D collagen type I gels. These cells are positive for both c‐erbB and retinoid receptors. Non‐malignant primary HMEC spontaneously formed branched structures in collagen, whereas SV40 large T antigen‐immortalized non‐tumorigenic MTSV1‐7 spontaneously formed balls and required heregulin or retinoid X receptor α‐selective retinoid Ro 25‐7386 for branching, which was further stimulated by combination of both types of agents. In malignant cells, heregulin alone induced ball formation and cooperated either with Ro 25‐7386 (T47D) or with retinoic acid receptor α‐selective AM580 (SKBR‐3) for branching morphogenesis, which was accompanied by changes in the subcellular distribution of α<jats:sub>2</jats:sub>β<jats:sub>1</jats:sub>‐integrin and E‐cadherin, and by down‐regulation of c‐erbB‐2, ‐3, or ‐4. Heregulin and/or retinoids correspondingly increased the integrin‐dependent adhesion of malignant cells to type I collagen. Our data demonstrate cooperative signaling of c‐erbB and retinoid receptor pathways at the levels of morphogenesis and immunophenotypic differentiation. © 2003 Wiley‐Liss, Inc.</jats:p>