Cytokeratin 5 determines maturation of the mammary myoepithelium
Vivi Deckwirth,
Eeva Kaisa Rajakylä,
Sandhanakrishnan Cattavarayane,
Anna Acheva,
Niccole Schaible,
Ramaswamy Krishnan,
Juan José Valle-Delgado,
Monika Österberg,
Pia Björkenheim,
Antti Sukura,
Sari Tojkander
Affiliations
Vivi Deckwirth
Section of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, Finland
Eeva Kaisa Rajakylä
Section of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, Finland
Sandhanakrishnan Cattavarayane
Section of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, Finland
Anna Acheva
Section of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, Finland
Niccole Schaible
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Ramaswamy Krishnan
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Juan José Valle-Delgado
Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo 00076, Finland
Monika Österberg
Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo 00076, Finland
Pia Björkenheim
Veterinary Teaching Hospital, University of Helsinki, Helsinki 00014, Finland
Antti Sukura
Section of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, Finland
Sari Tojkander
Section of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, Finland; Corresponding author
Summary: At invasion, transformed mammary epithelial cells expand into the stroma through a disrupted myoepithelial (ME) cell layer and basement membrane (BM). The intact ME cell layer has thus been suggested to act as a barrier against invasion. Here, we investigate the mechanisms behind the disruption of ME cell layer. We show that the expression of basal/ME proteins CK5, CK14, and α-SMA altered along increasing grade of malignancy, and their loss affected the maintenance of organotypic 3D mammary architecture. Furthermore, our data suggests that loss of CK5 prior to invasive stage causes decreased levels of Zinc finger protein SNAI2 (SLUG), a key regulator of the mammary epithelial cell lineage determination. Consequently, a differentiation bias toward luminal epithelial cell type was detected with loss of mature, α-SMA-expressing ME cells and reduced deposition of basement membrane protein laminin-5. Therefore, our data discloses the central role of CK5 in mammary epithelial differentiation and maintenance of normal ME layer.
